Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Aflibercept

Levoleucovorin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

5 Fluorouracil/Leucovorin/Irinotecan/Aflibercept

5 Fluorouracil: 400mg/m2, bolus infusion in \<5min followed by 5 Fluorouracil: 2400mg/m2, i.v in 46 hours continuous infusion (cycle repeated every two weeks)

5 Fluorouracil

Leucovorin: 400mg/m2, i.v in 2 hours infusion (cycle repeated every two weeks)

Irinotecan: 180mg/m2, i.v in 90min infusion (cycle repeated every two weeks)

Aflibercept: 4mg/kg i.v in 1 hour infusion (cycle repeated every two weeks)

John Souglakos, MD

Athanasios Kotsakis, MD

Investigators propose to study the combination of m FOLFIRI plus Aflibercept in a Phase II trial of patients with metastatic colorectal cancer. The promising results of aflibercept derived from preclinical studies and from clinical trials conducted in patients with refractory of recurrent to oxaliplatin-based 1st line treatment in patients with mCRC open the field to explore such therapeutic approaches in the 1st line setting in combination with the FOLFIRI regimen.

Colorectal cancer accounts for 8% of all malignant tumors in adults and is considered as a major cause of cancer morbidity and mortality worldwide. Although curative surgical resection is possible in 70-80% of patients at diagnosis, almost half of them will develop local or/and metastatic recurrence and will die of the disease with the liver been the most common site of metastatic spread from CRC.

Combinations of infusional administrated 5-fluorouracil/Leucovorin with irinotecan or oxaliplatin are accepted as the mainstay of first-line treatment and have increase the median overall survival of patients with advanced CRC from 12 months to about 21-22 months. In addition, resection for colorectal metastases (mainly in the liver), has become the standard of care, for patients with limited metastatic disease confounded to the liver and currently remains the only potentially curative therapy Aflibercept, also known as vascular endothelial growth factor (VEGF) Trap, is an angiogenesis inhibitor with a unique mechanism of action. Aflibercept is a recombinant fusion protein that consists of portions of human VEGFR1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A, as well as VEGF-B and placental growth factor, additional angiogenic growth factors that appear to play a role in tumor angiogenesis and inflammation. Aflibercept has been shown to bind VEGF-A, VEGF-B, and placental growth factor (PlGF) with higher affinity than their native receptors. In vitro and in vivo studies have shown that aflibercept can inhibit new vessel growth and tumor vascularization in tumor models.

Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line Treatment

A Open Label, Non Randomized, Phase Two Trial in Metastatic Colorectal Cancer (mCRC) With the Combination of m FOLFIRI Plus Aflibercept as First Line Treatment: MINOAS Trial

From date of randomization until the date of last follow up or death from any cause, assessed up to 100 weeks

Hellenic Oncology Research Group

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carboplatin

Gemcitabine

Carboplatin: 2.5 AUC i.v on day 1. Cycle repeated ever 2 weeks

Gemcitabine: 1100 mg/m2, iv on day 1. Cycle repeated every 2 weeks

Lambros Vamvakas, MD

Athanasios Karambeazis, MD

The investigators propose to study the safety and efficacy of the combination of Carboplatin plus Gemcitabine in a Phase I/II trial of elderly subjects with non-small cell lung cancer.

About 50% of newly diagnosed cases of NSCLC concern patients older than 65 years, while 30-40% of cases are diagnosed in patients older than 70 years. Furthermore, recent data suggest that during the last decade, the incidence and mortality of NSCLC has decreased in younger patients, while it has increased among older patients. Based on these observations, it becomes clear that NSCLC represents a significant health problem in elderly patients. However, elderly patients are frequently underrepresented in clinical trials evaluating new treatments in NSCLC. Indeed, more than 75% of patients older than 65 years with metastatic NSCLC never receive any kind of chemotherapy in the daily clinical practice.

In elderly patients there is lack of prospective data regarding the role of platinum-based doublets. It is not clear whether elderly patients gain any survival benefit or not from platinum-based doublets and whether these chemotherapeutic regimens result in a significant increase in toxicity.

There is a clear need to prospectively evaluate the tolerability and efficacy of platinum-based doublets as first-line chemotherapy for older NSCLC patients.

On this basis it would be very interesting to initiate a phase I/II study with gemcitabine/carboplatin combination as first line treatment in older NSCLC patients.

Carboplatin Plus Gemcitabine for Elderly Patients With Stage IV NSCLC

A Phase I/II Trial of the Carboplatin/Gemcitabine Combination as First Line Treatment for Elderly Patients With Stage IV NSCLC.

Disease control rate is defined as the proportion of patients with complete response or partial response or stable disease for at least 16 weeks

Patients will be evaluated for Adverse Events (related or unrelated to the treatment) on Day 1 of each cycle (cycle repeated every 2 weeks) up to 12 weeks from the date of first dose administration

Bevacizumab

Docetaxel

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Docetaxel: 60mg/m2 i.v on day 1. Cycle repeated ever 3 weeks

Bevacizumab: 7.5 mg/kg, iv on day 1. Cycle repeated every 3 weeks

The investigators propose to study the efficacy and safety of the combination of Docetaxel plus Bevacizumab in a Phase II trial of elderly subjects with non-small cell lung cancer

About 50% of newly diagnosed cases of NSCLC concern patients older than 65 years, while 30-40% of cases are diagnosed in patients older than 70 years. Furthermore, recent data suggest that during the last decade, the incidence and mortality of NSCLC has decreased in younger patients, while it has increased among older patients. Based on these observations, it becomes clear that NSCLC represents a significant health problem in elderly patients. However, elderly patients are frequently underrepresented in clinical trials evaluating new treatments in NSCLC. Indeed, more than 75% of patients older than 65 years with metastatic NSCLC never receive any kind of chemotherapy in the daily clinical practice.

According to retrospective data,the addition of bevacizumab to a standard, platinum-based chemotherapy regimen improves overall survival in patients with advanced non-squamous-cell, non-small-cell lung cancer and a good ECOG performance status. In addition, bevacizumab prolongs progression-free survival and improves response rate.

In elderly patients there is a complete lack of prospective data regarding the role of bevacizumab. It is not clear whether elderly patients gain any survival benefit or not and if the addition of bevacizumab to standard chemotherapeutic regimens results in a significant increase in toxicity.

There is a clear need to prospectively evaluate the tolerability of bevacizumab when added to standard first-line chemotherapy of elderly NSCLC patients. Therefore, the investigators propose to study the efficacy in elderly (\>70 years) patients treated with cytotoxic chemotherapy in combination with bevacizumab in the context of 1st line treatment.

Docetaxel Plus Bevacizumab for Elderly Patients With Stage IV NSCLC

First Line Treatment of Elderly Patients With Advanced or Metastatic NSCLC With Docetaxel and Bevacizumab

Patients will be evaluated for Adverse Events (related or unrelated to the treatment) on Day 1 of each cycle (cycle repeated every 3 weeks) up to 18 weeks from the date of first dose administration

Oxaliplatin

Panitumumab

botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}

Botensilimab

Balstilimab

400 mg/m2 IV bolus + 2,400 mg/m2 IV (over 46 hours) every 2 weeks

Emily Bolch

Nicholas C. DeVito, MD

This is a single-arm, interventional, pilot clinical trial. Fifteen evaluable patients will have tumor-informed ctDNA testing at baseline and start botensilimab and balstilimab treatment. They will receive botensilimab and balstilimab in 6-week cycles until progression, after which mFOLFOX6 and bevacizumab or panitumumab will be added to the regimen. Subjects will have safety testing at baseline and every two weeks while on study drug. Study treatment with botensilimab and balstilimab, mFOLFOX6, and bevacizumab or panitumumab will be continued until radiographic or clinical progression, toxicity, or patient withdrawal. Subjects will have one safety follow up visit 30 days after the last treatment and will be followed for survival every 12 weeks for up to 2 years.

3.1 Study Description

This is a single-arm, interventional, pilot clinical trial. Subjects with newly diagnosed, metastatic or unresectable, microsatellite stable colorectal cancer without liver, bone, or brain metastases will undergo tumor-informed ctDNA collection then start study treatment with botensilimab and balstilimab alone. They will have restaging scans every 12 weeks and will have ctDNA and CEA repeated at every cycle. When the subject experiences radiographic progression per RECIST/iRECIST or clinical progression per investigator's assessment, mFOLFOX6 and either bevacizumab or panitumumab will be added to the study drug regimen. Subject will continue on the new combination until radiographic or clinical progression, intolerable toxicity, or patient withdrawal.

No more than 20 subjects will be enrolled to ensure the trial obtains 15 evaluable subjects. All patients will be enrolled at the Duke Cancer Institute.

* Enrolled subjects are defined as subjects who give informed consent.
* Screen failures are defined as subjects who give informed consent and do not meet eligibility criteria.
* Accrued subjects are defined as subjects who give informed consent and meet eligibility criteria.

  * Withdrawal: Subject accrued but later withdrawn from the study, either before or after receiving a study drug.
  * Evaluable: All subject who are accrued, receive all Cycle 1 study treatment with botensilimab and balstilimab, and complete the first cycle of safety assessments will be considered evaluable for the primary endpoints for disease control rate, best overall response, and safety.
  * Non-evaluable: Subjects who accrued but did not complete the first cycle of safety assessments due to reasons other than study treatment-attributed toxicity (e.g., disease progression or inter-current illness) are considered non-evaluable for safety and efficacy.

Study Treatment Botensilimab 75 mg IV Every 6 weeks for up to 4 doses Balstilimab 240 mg IV Every 2 weeks Oxaliplatin 85 mg/m2 IV Every 2 weeks Leucovorin 400 mg/m2 IV Every 2 weeks Fluorouracil 400 mg/m2 IV bolus Every 2 weeks Fluorouracil 2400 mg/m2 IV Every 2 weeks (over 46 hours) Bevacizumab 5 mg/kg IV Every 2 weeks Panitumumab 6 mg/kg IV Every 2 weeks

5.1 Screening Period

During the screening period, subjects are consented and screened for the study. Informed consent must be obtained before initiation of any screening procedure that is performed solely for the purpose of determining eligibility for this study. Evaluations performed as part of routine care before informed consent can be considered as screening evaluations if done within the defined screening period, and if permitted by the local institutional review board (IRB) policies. Study eligibility is based on meeting all of the inclusion criteria and none of the exclusion criteria before the first dose of study drug on Cycle 1 Day 1.

The following study procedures must be done within 28 days prior to Cycle 1 Day 1:

* Inclusion and exclusion criteria
* Demographics
* Medical and cancer history
* Physical examination
* Height
* Vital signs and weight
* Concomitant medications
* CT and/or MRI of chest, abdomen, and pelvis
* ctDNA
* CEA
* PT/INR (prior to fresh tissue biopsy)
* Fresh tissue biopsy
* Archived tissue collection
* Tuberculosis (TB) test

  * NOTE: skin test is not allowed. Interferon-Gamma Release Assay (IGRA)-based tests such as QuantiFERON TB Gold and T-Spot TB tests are acceptable.

The following study procedures must be done or repeated within 7 days prior to Cycle 1 Day 1:

* CBC with differential
* CMP
* TSH and fT4
* Pregnancy test (only for women of childbearing potential)

Subject eligibility is determined using lab results obtained up to 7 days prior to Cycle 1 Day 1. Any laboratory assessments repeated on Cycle 1 Day 1 must meet eligibility requirements. The screening period ends upon receipt of the first dose of study drug or final determination that the subject is ineligible for the study.

5.2 Treatment Period

During the treatment period, subjects will receive botensilimab every 6 weeks for up to 4 doses and balstilimab every 2 weeks for up to 2 years. Following progression on the doublet, mFOLFOX6 will be administered every 2 weeks. Investigators will choose between bevacizumab and panitumumab, which will be administered every 2 weeks. Cycle length is every 6 weeks, with study visits occurring every 2 weeks. A treatment window of ± 1 day is allowed for day 1 of cycle 2 and all subsequent cycles. The treatment period lasts until: 1) subject has been receiving balstilimab for 2 years; 2) disease progression; 3) the occurrence of unacceptable treatment-attributed toxicity; or 4) other reasons for subject discontinuation as described in Section 5.7. Toxicity-attributed dose modifications of any of the study drugs may occur during the Treatment Period.

After the completion of the first cycle, laboratory assessments may be obtained up to 1 day prior to treatment. If necessary, the treatment visit may be within ± 1 day of the scheduled day 1 for cycle 2 and all subsequent cycles. If clinically indicated, additional visits and/or safety assessments may be warranted.

The following study procedures must be completed on days 1, 15, and 29 of each cycle:

* Concomitant medications
* Physical examination
* Vital signs and weight
* ECOG performance status
* CBC with differential
* CMP
* Administer balstilimab
* Administer mFOLFOX6
* Administer bevacizumab (if applicable)
* Administer panitumumab (if applicable)
* Adverse event assessment

The following study procedures must be added to the above test/procedures on Day 1 of each cycle:

* ctDNA
* CEA
* Administer botensilimab (maximum 4 doses)
* Plasma for biomarker analysis (prior to treatment on C1D1 and C3D1 only)

The following study procedures must be completed every 12 weeks (±1 week):

* Thyroid function tests (TSH and fT4)
* Tumor assessment (CT and/or MRI scans)

The following study procedures must be completed at time of progression on doublet therapy (any time prior to the start of chemotherapy administration):

* Optional biopsy of the progressing lesion
* PT/INR (only if doing biopsy, prior to biopsy)

Restaging scans will be performed every 12 weeks and disease response will be assessed using guidelines described in Section 5.6. The treatment period ends when a subject receives his or her last dose of study treatment; the subject then enters the follow-up period.

5.3 Follow-up Period

Subjects should return 30 (±7) days after their last dose of study drug for an end-of-treatment visit to complete the following study procedures:

* Concomitant medications
* Physical examination
* Vital signs and weight
* ECOG performance status
* Adverse event assessment
* CBC with differential
* CMP
* Thyroid profile (TSH and fT4)
* Serum pregnancy test (only for women of childbearing potential)
* ctDNA
* CEA
* Plasma for biomarker analysis

Subjects will have a telephone visit with the study team at 90 (+/-7) days after the last dose of study drug to complete an AE assessment. Any delayed irAEs must be reported to the principal investigator. Subjects with adverse events (AEs) attributed to study drug that are ongoing at the time of this 90-day safety follow-up visit will continue to be followed unless the AE is deemed unresolvable or the subject has started a new anti-cancer treatment regimen.

For subjects who are discontinued from study treatment for reasons other than disease progression, subjects will have disease status (blood tumor markers and restaging scans per standard of care schedule) followed until disease progression or start of new anti-cancer treatment regimen. Disease status may be collected via personal interviews or review of medical records.

Subjects will be followed for survival up to 2 years after discontinuing the study drug regimen or until the study is closed (whichever comes first). Survival status may be collected by phone call or review of medical or public records every 12 (±2) weeks.

5.4 Laboratory Assessments

Local laboratories will perform all clinical laboratory tests using standard procedures, and results will be provided to the investigator. Abnormalities in clinical laboratory tests that lead to a change in subject management (e.g., dose modification, requirement for additional medication, treatment or monitoring) are considered clinically significant for the purposes of this study and will be recorded on the case report form (CRF). If laboratory values constitute part of an event that meets criteria defining it as serious, the event (and associated laboratory values) must be reported as a serious adverse event (SAE).

5.5 Adverse Event Assessment

AEs will be documented throughout the study. AE seriousness, grade, and relationship to study drug will be assessed by the investigator using NCI-CTCAE version 5.0.

5.6 Tumor Assessments

Tumor response will be assessed using RECIST v.1.1 and iRECIST. Radiographic imaging will be performed with CT scan of chest/abdomen/pelvis with and without contrast and/or MRI scan of abdomen/pelvis every 12 weeks. The same method for tumor assessment should be employed at every assessment.

5.7 Subject Discontinuation

Subjects will receive study treatment until treatment discontinuation for one of the reasons listed below. However, subjects may discontinue study treatment or withdraw their consent to participate in the study at any time without prejudice. All reasons for discontinuation or withdrawal from trial will be recorded.

Subjects who progress on the initial doublet regimen do not have to discontinue study treatment at that time. Rather, they will add mFOLFOX6 and either bevacizumab or panitumumab and continue on study treatment. Patients who have complete response or prolonged stable disease may also elect to end study therapy after a discussion with their treating physician and with approval of the principal investigator. Reasons for subject discontinuation may include, but are not limited to, the following:

* Subject has been receiving balstilimab for 2 years
* Death
* Confirmed radiographic disease progression after switching to the botensilimab and balstilimab plus chemo/bev/pmab

  * Subjects with radiographic disease progression who are continuing to derive clinical benefit from the regimen may be allowed to continue on treatment beyond radiographic progression if, in the opinion of the investigator, it is the best interests of the patient, and with the principal investigator's approval.
* Significant noncompliance by subject or investigator
* Investigator or principal investigator determination that it is no longer safe and/or no longer in the subject's best interest to continue participation
* Withdrawal of consent
* Loss to follow-up
* Necessity for treatment with other anticancer treatment prohibited by protocol
* Sexually active subjects who refuse to follow the contraceptive guidelines
* Women who become pregnant or are breast feeding
* Request by regulatory agencies for termination of treatment of an individual subject or all subjects under the protocol
* Discontinuation of treatment may be considered for participants who have attained a confirmed complete response (CR)

Botensilimab and Balstilimab Optimization in Colorectal Cancer

Botensilimab and Balstilimab Optimization in Colorectal Cancer (BBOpCo)

Disease control rate is defined as the proportion of subjects who have a complete response, partial response, or stable disease at the time of a second restaging scan. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease is defined as a decrease of less than 30% or an increase of less than 20%. Increases of 20% or greater must be confirmed 4-8 weeks later, and confirmation scans must also show an increase of at least 5 mm in the sum of lesion sizes or an increase in the number of lesions. Otherwise, the increase will be counted as stable disease.

The number of subjects who went on treatment and had a complete response or partial response sometime during the study (prior to progression) divided by the number of subjects who went on treatment.

Disease control rate is defined as the proportion of subjects who have a complete response, partial response, or stable disease at the time of a second restaging scan. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease is defined as a decrease of less than 30% or an increase of less than 20%.

Months from treatment start date until the date of death from any cause.

Months from treatment start date until the date of first documented radiographic progression or date of death from any cause (whichever is first). Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Gateway for Cancer Research

Agenus Inc.

Nicholas DeVito, MD

Assistant Professor of Medicine

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Taxane

Patients who are going to receive chemotherapy plus Avastin (bevacizumab)

Vassilis Georgoulias, MD

Investigators propose to assess,the safety and tolerability profile (number of participants with adverse events)of bevacizumab (Avastin) when combined with standard chemotherapy as first line treatment of patients with metastatic Breast Cancer.

Nowadays in clinical practice patients with previously untreated metastatic breast cancer often receive taxane-based chemotherapy (paclitaxel or docetaxel) in combination with bevacizumab as it has been shown to increase progression-free survival. There is currently minimal information whether bevacizumab should be given as maintenance therapy after discontinuation of chemotherapy.

Maintenance Bevacizumab or Observation After Taxane Based First Line Chemotherapy In Metastatic Breast Cancer

Maintenance Bevacizumab or Observation After Taxane Based First Line Chemotherapy Plus Bevacizumab in Women With HER2-Negative Metastatic Breast Cancer. An Observational Study.

In this observational study investigators are going to assess standard schedules in which administration was every 2 or 3 weeks

In this observational study investigators are going to assess standard schedules in which the disease evaluation was performed every 3 or 6 weeks

Nazartinib

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations will be administered escalated doses of EGF816 orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study. The starting dose for the Phase I part first cohort of patients will be 75 mg once per day capsule.

Treatment naïve participants with locally advanced or metastatic NSCLC harboring EGFR mutations will be administered with EGF816 at RP2D during Phase II part of the study.

EGF816 will be dosed once daily. On the first day of each treatment cycle, the patient receives an adequate drug supply for self-administration at home. The investigator will instruct the patient to take EGF816 exactly as prescribed.

EGF816

Novartis Pharmaceuticals

This is a Phase I/II, multi-center, open-label study, composed with a Phase I part (dose-escalation phase) followed by a Phase II part (expansion phase).

The dose escalation phase was designed to determine as primary objective the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of EGF816 monotherapy in adult subjects with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC harboring specific EGFR mutations. Patients may have or not have received prior lines of antineoplastic therapy. An adaptive Bayesian Logistic Regression Model (BLRM) employing the escalation with overdose control (EWOC) principle will be used during the dose escalation part for dose level selection and MTD recommendation. The primary objective of the Phase II part is to estimate antitumor activity of EGF816 as measured by overall response rate (ORR) determined by Blinded Independent Review Committee (BIRC) assessment in accordance to RECIST 1.1.

Following completion of screening procedures and confirmation of patient eligibility, the participants are enrolled in the study. The study treatment begin on Cycle 1, Day 1 with the first administration of EGF816. A treatment cycle is defined as 28 days. Oral EGF816 is administered once daily on a continuous schedule until patient experiences unacceptable toxicity, progressive disease (PD), and/or treatment is discontinued at the discretion of the investigator, patient withdrawal of consent, or due to any other reasons. Treatment with EGF816 may be continued beyond RECIST 1.1 defined PD, if, in the judgment of the investigator, there is evidence of clinical benefit and the patient wishes to continue with the study treatment.

A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Number of participants with DLTs during the first 28 days of therapy. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with EGF816 and meets any of the criteria described in the protocol. A participant with multiple occurrences of DLTs under one treatment is counted only once.

ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined by BIRC assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1

DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1

To characterize the PK properties of EGF816 and metabolite LMI258, Cmax will be calculated (Phase I \& II parts)

To characterize the PK properties of EGF816 and metabolite LMI258, Tmax will be calculated (Phase I \& II parts)

To characterize the PK properties of EGF816 and metabolite LMI258, AUCtau will be calculated (Phase I \& II parts)

Changes in EGFR signaling pathway of newly obtained tumor samples following EGF816 treatment will be evaluated by IHC of three pharmacodynamics (PD) biomarkers: p-EGFR, p-AKT and p-ERK. The assigned H-score semi-quantitatively assesses the expression level of these protein markers and their phosphorylated forms.

ORR is defined as proportion of patients with best overall response of PR+CR determined by Investigator assessment in accordance to RECIST 1.1

DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1

TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1

Assessment of the tolerability of EGF816 will be performed continuously during the treatment phase

DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by BIRC in accordance to RECIST 1.1

DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by BIRC in accordance to RECIST 1.1

PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by BIRC in accordance to RECIST 1.1

TTR is defined as as the time from the date of first dose of study treatment to the date of first documented response (CR or PR) determined by by BIRC in accordance to RECIST 1.1

OS is defined as the time from first dose of the study treatment to the date of death due to any cause.

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 75 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 75 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 100 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 100 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 150 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 150 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 200 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 200 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 225 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 225 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 300 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 300 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 350 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 350 mg (Phase I Part)

Treatment naïve participants with locally advanced or metastatic NSCLC harboring EGFR mutations were administered with 150 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase II part of the study.

EGF816 150 mg (Phase II Part)

All Subjects

Total

Age, Categorical

Sex: Female, Male

Race/Ethnicity, Customized

Study Director

Dose-determining set (DDS) including all patients who received at least one dose of EGF816 in the dose escalation phase who had met the minimum safety evaluation requirements (observed for ≥ 28 days following the first dose) and the minimum exposure criterion (at least 75% of the planned doses of EGF816) or discontinue earlier due to DLTs

Number of Participants With Dose Limiting Toxicities (DLTs) (Phase I Part)

Full Analysis Set (FAS) including participants who received at least one dose of EGF816

Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) (Phase II Part)

Progression-free Survival (PFS) by Investigator Assessment (Phase I & Phase II Parts)

Duration of Response (DOR) by Investigator Assessment (Phase I & II Parts)

Observed Maximum Plasma Concentration (Cmax) of EGF816 and Metabolite LMI258 (Phase I & Phase II Part)

Time to Maximum Plasma Concentration (Tmax) of EGF816 and Metabolite LMI258 (Phase I & Phase II Part)

Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) of EGF816 and Metabolite LMI258 (Phase I & Phase II Part)

Change From Baseline in H-score for Immunohistochemistry (IHC) Biomarkers From Tumor Tissue Samples (Phase I Part)

Overall Response Rate (ORR) by Investigator Assessment (Phase I & II Parts)

Disease Control Rate (DCR) by Investigator Assessment (Phase I & II Parts)

Time to Response (TTR) by Investigator Assessment (Phase I & II Parts)

Number of Participants With Dose Interruptions and Dose Reductions (Phase I & II Parts)

Duration of Response (DOR) by BIRC (Phase II Part)

Disease Control Rate (DCR) by BIRC (Phase II Part)

Progression-Free Survival (PFS) by BIRC (Phase II Part)

Time to Response (TTR) by BIRC (Phase II Part)

Overall Survival (OS) (Phase II Part)

Overall Study

Patients who have either received or who are going to receive chemotherapy plus Avastin (bevacizumab)

Investigators propose to assess, retrospectively and prospectively the safety and tolerability profile (number of participants with adverse events) of standard chemotherapy and anti-angiogenic agent bevacizumab (Avastin) as first line treatment of patients with advanced or metastatic Non Small Cell Lung Cancer.

All treatment schedules that are going to be assessed are considered by the international guidelines as standard therapy for patients with advanced or metastatic Non Small Cell Lung Cancer.

In addition investigators propose to assess the compliance of patients to treatment and the efficacy of treatment. That means percentage of objective responses, duration of response, progression free survival and estimation of overall survival

Bevacizumab Plus Chemotherapy for Advanced Non Small Cell Lung Cancer Patients as 1st Line Treatment

Assessment of Clinical Practice Administration of Chemotherapy and Anti-angiogenic Agent (Bevacizumab) Retrospectively and Prospectively as First Line Treatment for Patients With Advanced or Metastatic Non Small Cell Lung Cancer. Assessment of Toxicity, Compliance and Survival of Patients.

In this observational study investigators are going to assess standard schedules in which administrations were every 3 weeks.

In this observational study investigators are going to assess standard schedules in which the disease evaluation was performed every 6 weeks

Investigators propose to assess, retrospectively (from 1/7/2009) and prospectively (up to 31/12/2013,) the safety and tolerability profile (number of participants with adverse events) of standard chemotherapy and anti-angiogenic agent bevacizumab (Avastin) as first line treatment of patients with metastatic Colorectal Cancer with or without KRAS mutation. All treatment schedules that are going to be assessed are considered by the international guidelines as standard therapy for patients with metastatic Colorectal Cancer.

In addition investigators propose to assess the compliance of patients to treatment and the efficacy of treatment. That means percentage of objective responses, duration of response, frequency of curative liver resection after the administration of treatment, progression free survival and estimation of overall survival

Assessment of Clinical Practice Administration of Chemotherapy and Anti-angiogenic Agent (Bevacizumab) in Colorectal Cancer

Assessment of Clinical Practice Administration of Chemotherapy and Anti-angiogenic Agent (Bevacizumab) Retrospectively (From 1/7/2009) and Prospectively (up to 31/12/2013) as First Line Treatment for Patients With Locally Advanced or Metastatic Colorectal Cancer (With or Without KRAS Mutation). Assessment of Toxicity, Compliance and Survival of Patients.

In this observational study investigators are going to assess standard schedules in which administration was every 2 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line Treatment	NCT02624726	Metastatic Colo...	5 Fluorouracil Leucovorin Irinotecan Aflibercept	18 Years -	Hellenic Oncology Research Group
Carboplatin Plus Gemcitabine for Elderly Patients With Stage IV NSCLC	NCT02175381	NSCLC	Carboplatin Gemcitabine	70 Years -	Hellenic Oncology Research Group
Docetaxel Plus Bevacizumab for Elderly Patients With Stage IV NSCLC	NCT02179567	NSCLC	Docetaxel Bevacizumab	70 Years -	Hellenic Oncology Research Group
Botensilimab and Balstilimab Optimization in Colorectal Cancer	NCT06268015	Colorectal Canc...	Botensilimab Balstilimab Oxaliplatin Leucovorin Fluorouracil Bevacizumab Panitumumab	18 Years -	Duke University
Maintenance Bevacizumab or Observation After Taxane Based First Line Chemotherapy In Metastatic Breast Cancer	NCT01978977	Metastatic Brea...		18 Years -	Hellenic Oncology Research Group
A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies	NCT02108964	Advanced Non-sm...	EGF816	18 Years -	Novartis
Carboplatin Plus Gemcitabine for Elderly Patients With Stage IV NSCLC	NCT02175381	NSCLC	Carboplatin Gemcitabine	70 Years -	Hellenic Oncology Research Group
Bevacizumab Plus Chemotherapy for Advanced Non Small Cell Lung Cancer Patients as 1st Line Treatment	NCT01934465	Non Small Cell ...		18 Years -	Hellenic Oncology Research Group
Assessment of Clinical Practice Administration of Chemotherapy and Anti-angiogenic Agent (Bevacizumab) in Colorectal Cancer	NCT01811108	Metastatic Colo...		18 Years -	Hellenic Oncology Research Group
Botensilimab and Balstilimab Optimization in Colorectal Cancer	NCT06268015	Colorectal Canc...	Botensilimab Balstilimab Oxaliplatin Leucovorin Fluorouracil Bevacizumab Panitumumab	18 Years -	Duke University
Carboplatin Plus Gemcitabine for Elderly Patients With Stage IV NSCLC	NCT02175381	NSCLC	Carboplatin Gemcitabine	70 Years -	Hellenic Oncology Research Group

Spots Global Cancer Trial Database for 1st line

Every month we try and update this database with for 1st line cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for 1st line

Every month we try and update this database with for 1st line cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for 1st line cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.