Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Osimertinib

Mitogens

Amivantamab-vmjw

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

Participants will receive osimertinib and amivantamab.

Osimertinib will be administered as 80 mg oral tablet once daily (from Day 2) until progression of disease or until a study intervention discontinuation criterion is met.

Amivantamab will be administered as an IV infusion at 1050 mg (\< 80 kg body weight) or 1400mg (≥ 80 kg body weight) (in 28-day cycles: once weekly in Cycle 1 (with a split dose on Days 1 to 2) and then every 2 weeks in subsequent cycles) until progression of disease or until a study intervention discontinuation criterion is met. The first cycle dose is spilt over 2 days- 350 mg on day 1 and 700 mg \[body weight \< 80 kg\] or 1050 mg \[body weight ≥ 80 kg\] on day 2.

Amivantamab

AstraZeneca Clinical Study Information Center

This study will assess the safety and efficacy of Osimertinib with Amivantamab as First-line Treatment in Participants with Epidermal Growth Factor Receptor Mutation-Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC).

This is a Phase II, open-label, single-arm, multi-centre study to assess the safety and efficacy of osimertinib with amivantamab as first-line treatment in adult participants with a local preexisting positive approved tissue test result for EGFRm (Ex19del or L858R), locally advanced (clinical stage IIIB, IIIC), metastatic (clinical stage IVA or IVB), or recurrent non-squamous NSCLC.

This study consists of screening period of 28 days, followed by the study intervention period wherein the participant receives treatment from Day 1 until disease progression or study intervention discontinuation. Participants will be followed up at week 6 (± 1 week), week 12 (± 1 week), then every 12 weeks (± 1 week) until radiological disease progression. Survival follow up will be performed every 12 weeks. Upon study intervention discontinuation a 28 day follow up visit will be performed.

A Study to Investigate Safety and Efficacy of Osimertinib and Amivantamab in Participants With Non-small Cell Lung Cancer With Common Epidermal Growth Factor Receptor Mutations

A Phase II, Open-label, Single-arm, Multi-centre Study to Evaluate the Safety and Efficacy of Osimertinib With Amivantamab as First-line Treatment in Participants With Epidermal Growth Factor Receptor Mutation-Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (OSTARA)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

To assess the safety and tolerability of osimertinib plus amivantamab in participants with EGFR mutation-positive, locally advanced, or metastatic NSCLC.

The time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause. The analysis will include all dosed participants. All events will be included, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1.

Time from date of first dose of study intervention until the date of death due to any cause. The analysis will include all dosed participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy.

The proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per RECIST 1.1. The analysis will include all dosed participants with measurable disease at baseline.

The time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause. The analysis will include all dosed participants with measurable disease at baseline who have a confirmed response.

Parexel

AstraZeneca

Micronutrients

Hematinics

Vitamins

Gemcitabine

Docetaxel

Carboplatin

Vinorelbine

Pemetrexed

Cisplatin

Lenograstim

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

This is a phase 2 clinical trial for patients with clinical Stage IB-III resectable and operable non-small cell lung cancer, evaluating whether the switch to an alternative, non-platinum neoadjuvant chemotherapy is safe and effective in patients who do not respond to neoadjuvant platinum-based chemotherapy. Those who fail to respond to platinum-based chemotherapy will be switched to the alternative neoadjuvant chemotherapy vinorelbine 45 mg/m2 and docetaxel 45 mg/m2 on day 1 followed by pegylated filgrastim on day 2, repeated every 2 weeks for 4 doses, followed by repeat FDG PET and CT scan.

pemetrexed

cisplatin

Gemcitabine Hydrochloride

Vinorelbine Tartrate

Jamie E. Chaft, MD

The purpose of this study is to test a new approach to the use of standard drugs before surgery in patients with lung cancer. This study will find out what effects, good and/or bad, that this approach has on the cancer.

It is routine to give chemotherapy prior to surgery in patients with this type of lung cancer, to help keep it from coming back. It is also routine to perform a special type of scan called a PET scan. This PET scan measures how active a cancer is by use of a special tracer made out of sugar. In this study, all patients will have a PET scan and then be treated with standard chemotherapy drugs, either pemetrexed and cisplatin if the cancer is a "non-squamous" cancer or gemcitabine and cisplatin if the cancer is a squamous cancer. In rare cases, the doctor will decide to give carboplatin instead of cisplatin. In most patients, a repeat PET scan will show that the tumor is decreasing and they will complete standard chemotherapy then go on to have surgery.

In some patients, a repeat PET scan will show that the tumor has not decreased enough. For these patients, the routine practice is to proceed with surgery. This research study will test whether switching from the standard treatment of pemetrexed and cisplatin or gemcitabine and cisplatin to a different treatment called vinorelbine and docetaxel is safe and effective. Vinorelbine and docetaxel are also standard chemotherapy drugs which work in a different way than pemetrexed or gemcitabine and cisplatin.

Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN)

Phase II Trial of Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN)

The primary endpoint was partial metabolic response after 2 cycles of "switch" therapy as assessed by PERCIST (SUVmax decrease ≥30% using the pre-switch scan as new baseline).

The percentage of patients with a major pathologic response

Eli Lilly and Company

United States Department of Defense

Memorial Sloan Kettering Cancer Center

There was not a comparative toxicity analysis done. CTCAE toxicities were collected for all patients. A comparative toxicity of those patients who switched versus those who did not was not seen as clinically relevant. Hematologic toxicities are anticipated with all chemotherapy.

Patients with clinical Stage IB-III resectable and operable non-small cell lung cancer

All Patients

Age, Categorical

Sex: Female, Male

Chaft, Jamie, MD

PERCIST Partial Metabolic Response

Pathologic Response Rate

Overall Study

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

Vitamin B 12

Hydroxocobalamin

Methylcobalamin

Vitamin B12

Cobalamin

Cyanocobalamin

Pemetrexed, 500mg/m2 + appropriate vitamin supplementation + Carboplatin \[Target AUC 5 IV infusion,based on Calvert formula,GFR estimated using estimated creatinine clearance per Cockcroft and Gault formula, obtained prior to each cycle\] + Antiemetic therapy at investigator's discretion.

Pemetrexed, 500mg/m2 + appropriate vitamin supplementation + Antiemetic therapy at investigator's discretion.

Pemetrexed, 500 mg/m2 + Pretreatment \[dexamethasone + vitamin B12 + folic acid, as per pemetrexed label\] + Antiemetic therapy at investigator's discretion.

Carboplatin \[Target AUC 5 IV infusion,based on Calvert formula,GFR estimated using estimated creatinine clearance per Cockcroft and Gault formula, obtained prior to each cycle\].

Carlos G Ferreira, PhD

Rogerio Lilenbaum, MD

Carlos Henrique E Barrios, MD

Carlos Augusto M. Beato, MD

José Rodrigues, MD

Yeni Neron, MD

André Murad, PhD

Ronaldo A Ribeiro, PhD

Fábio Franke, MD

Mauro Zukin, MD

Optimal management of patients with advanced NSCLC and with PS 2 remains controversial and underrepresented in clinical trials, typically accounting for 5 to 10% of enrolled patients. Patient PS 2 proportion in population-based studies is considerably higher than that included in clinical trials. Management of patients with PS of 2 in clinical practice is empirical and inconsistent. Patients have median overall survival of 3 to 5 months in randomized trials, and treatment options include best supportive care, single-agent and combination chemotherapy. Retrospective studies have suggested that patients PS 2 may benefit from first-line chemotherapy in terms of symptom improvement and overall survival. In many of these studies, single-agent chemotherapy was compared with best supportive care alone. Data on the role of cisplatin-based combinations for patients with PS 2 is more scant, with one study questioning its benefit, and another interrupting accrual because of undue toxicity. With regards to carboplatin, the Cancer and Leukemia Group B (CALGB) study 9730 compared paclitaxel plus carboplatin versus paclitaxel alone in a subgroup of 107 patients with PS 2; the median overall survival was significantly longer in group treated with combination chemotherapy (4.7 versus 2.4 months). Combination chemotherapy with carboplatin and paclitaxel also produced a statistically significantly higher incidence of severe hematological and non-hematological toxicities. On the basis of aforementioned results, a recent European panel stated that carboplatin-based or low-dose cisplatin-based doublets might represent alternative options to single-agent chemoterapy in patients PS 2. Outside clinical trials, single-agent chemotherapy with a 3rd generation agent remains valid option for patients PS2. Results demonstrate that pemetrexed is an agent with established single-agent activity in NSCLC, and suggest it is a potential candidate for combinations with platinum and other agents currently utilized for patients with advanced NSCLC. Favorable toxicity profile of pemetrexed suggests that this agent is an ideal candidate for single agent testing and in combination among patients with PS 2. Substantial doubt remains in the comparative benefit from monotherapy versus combination. Starting dose and schedule of pemetrexed were set for this study based on its current labeling in the 2nd line treatment of metastatic NSCLC and 1st line treatment of malignant pleural mesothelioma.

This is a Phase III, open label, randomized study to enroll 228 patients with advanced in a 1:1 ratio at the time of registration. Patients in Arm A will receive pemetrexed, 500 mg/m2, with appropriate vitamin supplementation; patients in Arm B will receive the same dose and schedule of pemetrexed as in Arm A, in combination with carboplatin, AUC of 5. For the purpose of the study, treatment (Arm A or Arm B) will consist of up to four cycles of therapy (repeated every 21 days). Primary endpoint of the study is overall survival; secondary endpoints include toxicity, response rate, and progression-free survival. At the time of analysis, patients will be stratified according to age (≥ 70 versus \< 70 years), disease stage (IIIB versus IV), site, and weight loss (≥ 5 Kg versus \< 5 Kg).

The dose of carboplatin will be determined according to the formula developed by Calvert et al., which is shown in equation \[1\] below and uses the estimated creatinine clearance according to the method of Cockcroft and Gault for estimation of the glomerular filtration rate (GFR) (equation \[2\] below):

1. Dose of carboplatin (mg) = Target AUC x (GFR + 25)
2. GFR = (140 - Age) x Weight/(72 x serum creatinine) (multiply by 0.85 in women) Sample Size and Expected Accrual In the CALGB 9730 study of advanced NSCLC, first-line treatment with paclitaxel plus carboplatin resulted in a median overall survival of 4.7 months among patients with a performance status of 2. In the ECOG 1594 study, the median overall survival of patients with a performance status of 2 who were treated with platinum-based doublets was 4.1 months. Approximately 208 eligible patients are needed to provide 80% power to detect a difference between the two treatment arms with a two-sided type I error of 0.05, assuming that pemetrexed plus carboplatin will result in a median survival of at least 4.3 months, and pemetrexed alone 2.9 months. An additional 20 patients will be accrued to account for an early dropout rate of 10%, for a total of 228 patients. It is anticipated that the accrual time will be approximately 22 months and patients will be followed for 1 year after completion of treatment; therefore, 2 years and 10 months will be needed to complete the study.

Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2

Phase III Trial of Single-Agent Pemetrexed (Alimta®) Versus the Combination of Carboplatin and Pemetrexed in Patients With Advanced Non-small-cell Lung Cancer and Performance Status of 2

Each patient will be followed from inclusion date in the study (ICF signature) until the death date for any cause, whichever came first, assessed up to one year after completion of study treatment. Primary objective of this study is to determine and compare the overall survival produced by pemetrexed as a single-agent and by the combination of pemetrexed plus carboplatin in a patient with previously untreated, advanced non-squamous NSCLC and an ECOG Performance status of 2.

Planned interim analysis for the 46 death events, and cut off for patients at V3 to V6, every 06 months as average. Patients with at least any study treatment dose were included in safety analyses, focused on toxicity grades 3-4. Toxicity evaluation from date of last treatment dose until 1 month of follow up visit date, and every cycle according CTCAE v3.0 for study dose adjustment as per guidelines based on episodes of febrile neutropenia; grade 4 thrombocytopenia and/or bleeding; and any grade 3 or 4 non-hematologic toxicity except nausea/emesis. Safety evaluation for medical conditions, symptoms or signs, laboratory parameters as per protocol criteria, disregarding disease progression when unrelated drugs or any procedure of study.

Progression free survival evaluated by RECIST criteria, as described in protocol. Time for Progression free survival will be measured from date of first treatment dose to either date a patient is first recorded as disease progression (even for a withdrawn patient due to toxicity), or the date of death due to any causes before progression. Patient lost of follow up will be censored from the last contact date. Patients starting new treatment before disease progression will be censored at that date of starting new treatment. A patient who dies without disease progression the time for this assessment will be last follow-up date.

Objective response rate evaluated by RECIST criteria as described in protocol. From those patients with tumoral response, the duration of response is measured from the date of first response evidence (Complete and Partial Responses) until first recorded as disease progression, or date of death to any causes before progression. Duration for tumoral response will be censored in the last follow up date for those patients with tumoral response who still alive and has not progressed.

Instituto Nacional de Cancer, Brazil

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

This is a Phase I/Ib, open-label, dose-escalation, multi-center, non-randomized study designed to evaluate the safety and tolerability of oral Binimetinib in combination with carboplatin and pemetrexed.

Phase I part A standard 3+3 dose-escalation will be used to determine the maximum administered dose (MAD) and the RP2D for the combination in subjects with advanced non-squamous lung carcinoma.

Phase Ib part Once RP2D has been identified, an expansion cohort will be accrued; these patients will be stratified by KRAS genotype.

The RP2D will be expanded by enrolling additional patients, stratified by KRAS genotype, to a total of 30 patients eligible for the safety set (including those treated at the same dose combination in the dose-escalation phase of the study who are eligible for the safety set) to be evaluated for safety, tolerability, pharmacokinetics and biologic activity of MEK162.

Continuous MEK162 with dose escalation until the Recommended Phase 2 dose (RP2D) one dose level below the Maximum administered dose (MAD) or progression of disease.

MEK162 tablets 15 mg strength will be taken orally on a BID dose schedule.

Binimetinib

4-6 cycles given intravenously in combination with carboplatin as per standard therapy.

4-6 cycles of intravenous Carboplatin in combination with Pemetrexed as per standard therapy.

Natasha Leighl, MD

Amit Oza, MD

MEK162 has shown significant inhibition of tumor growth as a single agent in NSCLC xenograft models in mice and human cancer cells in vitro, which have KRAS and/or other mutations. These data suggest that MEK162 may provide a potential benefit in cancer indications harboring these mutations. MEK162 is currently being investigated in phase I clinical testing and has been well tolerated up to an MTD of 45mg BID in cancer patients.

There has been little change in survival benefit for patients with non-small cell lung cancer in recent years. Emerging new treatment options relying on molecular and genetic markers are being studied extensively. Thus, there has been a shift to manage non-small cell lung cancer with molecular targeted therapies in combination with standard chemotherapy. This study will be targeting patients with KRAS mutations.

OBJECTIVES

1.1 Primary Objectives

* To assess the safety of MEK162 administered in combination with carboplatin and pemetrexed as first line treatment in advanced non-small cell lung cancer (NSCLC).
* To determine the recommended phase II dose (RP2D) of MEK162 to be used when given in a continuous dosing schedule together with pemetrexed and carboplatin administered on a 3-weekly schedule as first line treatment in advanced NSCLC.
* To explore the efficacy (as measured by tumor response in the Phase Ib portion) of the combination of MEK162 in addition to pemetrexed and carboplatin in treatment-naïve patients with EGFR wild-type, ALK-rearrangement negative NSCLC of the lung.

1.2 Secondary Objectives

* To characterize the population pharmacokinetics of MEK162 administered in combination with carboplatin and pemetrexed (Phase I).
* To explore relationships between KRAS mutation (and sub-types) and additional genomic mutations and objective clinical response.

1.3 Trial End-points Primary Phase I • Development of dose-limiting toxicity (DLT), (defined in section 4.3) as measured with NCI CTC AE v4.

Phase Ib

• Objective response rate (ORR) as per RECIST v1.1.

Secondary Phase I • Adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs.

Phase Ib

* Evaluation of response rate (RR), progression-free survival (PFS) and disease control rate (DCR) for patients with and without KRAS mutation in tumor tissue.
* Exploratory analysis of KRAS mutation sub-type.

Exploratory end-points

• A limited sampling strategy pharmacokinetic model will be used to ensure that the clearance of MEK162 is not influenced by the concurrent administration of pemetrexed-based chemotherapy.

A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung

Exploratory end-points

• A limited sampling strategy pharmacokinetic model will be used to ensure that the clearance of MEK162 is not influenced by the concurrent administration of pemetrexed-based chemotherapy.

• Evaluation progression-free survival (PFS) for patients with and without KRAS mutation in tumor tissue.

Number of weeks survived before progression or death.

To determine the recommended dose in milligrams per day of the combination of MEK162 with standard therapy pemetrexed and carboplatin as determined by toxicity.

The size of tumours in centimetres before and after treatment. The measurements will be compared against the RECIST v1.1 criteria to ascertain response as defined in the protocol.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Investigate Safety and Efficacy of Osimertinib and Amivantamab in Participants With Non-small Cell Lung Cancer With Common Epidermal Growth Factor Receptor Mutations	NCT05801029	Non-Small Cell ...	Osimertinib Amivantamab	18 Years - 130 Years	AstraZeneca
A Study to Investigate Safety and Efficacy of Osimertinib and Amivantamab in Participants With Non-small Cell Lung Cancer With Common Epidermal Growth Factor Receptor Mutations	NCT05801029	Non-Small Cell ...	Osimertinib Amivantamab	18 Years - 130 Years	AstraZeneca
Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN)	NCT01443078	Lung Cancer	pemetrexed cisplatin Carboplatin Gemcitabine Hyd... Vinorelbine Tar... Docetaxel	18 Years -	Memorial Sloan Kettering Cancer Center
Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2	NCT01836575	Non Small Cell ...	Pemetrexed Carboplatin	18 Years -	Instituto Nacional de Cancer, Brazil
A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung	NCT02185690	Lungcancer	Binimetinib Pemetrexed Carboplatin	18 Years - 90 Years	University Health Network, Toronto
Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2	NCT01836575	Non Small Cell ...	Pemetrexed Carboplatin	18 Years -	Instituto Nacional de Cancer, Brazil
A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung	NCT02185690	Lungcancer	Binimetinib Pemetrexed Carboplatin	18 Years - 90 Years	University Health Network, Toronto

Spots Global Cancer Trial Database for non squamous

Every month we try and update this database with for non squamous 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.