Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Trifluridine

Immunoglobulins

Antimetabolites

Antiviral Agents

Sym004 will be administered as a loading dose of 9 mg/kg on Cycle 1 Day 1, followed by weekly doses of 6 mg/kg beginning Cycle 1 Day 8.

TAS-102 is commercially available and will be administered as per local prescribing instructions.

Sym004 is a 1:1 mixture of two recombinant mAbs (futuximab and modotuximab) which bind specifically to non-overlapping epitopes located in the extracellular domain (ECD) of the EGFR.

Sym004

TAS-102 is a combination of trifluridine, a thymidine-based nucleic acid analogue, and tipiracil, a thymidine phosphorylase inhibitor.

TAS-102

Josep Tabernero, MD, PhD

This is a Phase 3, randomized, open-label, 2-arm trial designed to evaluate overall survival (OS) following treatment with Sym004, an investigational medicinal product (IMP), versus TAS-102 (trifluridine/tipiracil), a comparator (control) agent.

Randomization is in the ratio of 1:1 to either Sym004 (Arm A) or TAS-102 (Arm B) in genomically-selected patients with chemotherapy-refractory or relapsed metastatic colorectal carcinoma (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy.

Following consent, centralized genomic analysis will be conducted on blood samples obtained from each potential patient. Double-negative (DN) results as defined in trial inclusion criteria will be required for initial eligibility prior to randomization. Patients with DNmCRC will continue in the screening process. Once deemed fully eligible, patients will be randomized to either Arm A or Arm B (collectively referred to as protocol therapy).

Dosing cycles of 28 days with the assigned protocol therapy will continue until a protocol-specified discontinuation criterion is met. Following treatment discontinuation, patients will continue to be followed for OS.

Sym004 Versus TAS-102 in Patients With mCRC

A Phase 3, Randomized, Open-Label, Multicenter Trial of Sym004 Versus Trifluridine/Tipiracil (TAS-102) in Patients With Chemotherapy-Refractory or Relapsed Metastatic Colorectal Carcinoma and Acquired Resistance to Anti-EGFR Monoclonal Antibody Therapy

Time (in months) from the date of randomization to the date of death. In the absence of death confirmation or for patients alive as of the OS data cut-off date (i.e., date upon reaching 445 deaths), OS will be censored at the date of last study follow-up, or the cut-off date, whichever is earlier.

Time (in months) from the date of randomization until the date of the investigator-assessed radiological disease progression or death due to any cause.

Investigator-assessed radiological disease progression (per RECIST v1.1) with the following key censoring rules:

* Patients who are alive with no disease progression as of the analysis cut-off date will be censored at the date of the last tumor assessment.
* Patients who receive non-study cancer treatment before disease progression will be censored at the date of the last evaluable tumor assessment before the initiation of non-study cancer treatment.
* Patients with clinical, but not radiologic, evidence of progression will be censored at the date of the last evaluable tumor assessment before the clinical progression assessment.

Defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). Assessed approximately every 8 weeks (at the end of even-numbered cycles).

Defined as the proportion of patients with objective evidence of CR, PR, or stable disease (SD). Assessed approximately every 8 weeks (at the end of even-numbered cycles).

Time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, with the same censoring rules as for PFS.

AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology and the severity of the toxicities will be graded according to the Common Terminology Criteria for Adverse Events (Version 5) (CTCAE v5), where applicable, from signing of informed consent up to 30 days after the final dose of Sym004.

Serum sampling to assess the potential for ADA formation are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Day 1 of odd numbered cycles thereafter, the End of Treatment Visit, and the 1-Month Follow-up Visit.

Cmin is defined as the serum concentration at the start of infusion. The serum concentration of Sym004 is the sum of the two constituting mAbs, futuximab and modotuximab. Sparse sampling at 7 timepoints are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment Visit.

Cmax is defined as the serum concentration at the end of infusion. The serum concentration of Sym004 is the sum of the two constituting mAbs, futuximab and modotuximab. Sparse sampling at 7 timepoints are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment Visit.

Symphogen A/S

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Hyaluronic Acid

Nimesulide

0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 of a 28-day cycle

0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle

The preliminary RP2D of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle

CA102N is a covalently bound conjugate of the biological polymer sodium hyaluronate (NaHA) and nimesulide (Nim).

CA102N

LONSURF is a cytotoxic combination treatment of 2 new drugs: trifluridine, a thymidine-based nucleoside analog, and tipiracil, an inhibitor of thymidine phosphorylase.

LONSURF

Shubham Pant, MD

Study HS-CA102N-101 is a phase 1, two part (dose escalation, dose expansion), multicenter, non-randomized, open-label, multiple dose, first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF) in subjects with advanced solid tumors.

CA102N will be evaluated in subjects with locally advanced or metastatic solid tumours for which no effective therapy is available in Part 1 (dose escalation) and in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer (mCRC) after prior oxaliplatin and irinotecan-based chemotherapy in Part 2 (dose expansion).

Study HS-CA102N-101 is a phase 1, two part (dose escalation, dose expansion), multicenter, non-randomized, open-label, multiple dose, first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF) in subjects with advanced solid tumors.

Part 1 (dose escalation) will determine the safety and tolerability of three dose levels of CA102N as monotherapy and the safety, tolerability and preliminary recommended phase 2 dose (RP2D) of CA102N in combination with trifluridine/tipiracil (LONSURF) in patients with locally advanced or metastatic solid tumors.

Part 2 (dose expansion) will further investigate the safety and tolerability of the combination of CA102N and trifluridine/tipiracil (LONSURF) at the preliminary RP2D in patients with locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and if RAS wild-type metastatic colorectal cancer, an anti-epidermal growth factor receptor (EGFR) therapy..

Preliminary efficacy will be evaluated in Parts 1 and 2 of the study as an exploratory endpoint.

Part 1 (dose escalation) of the study will use a conventional 3+3 design (3 subjects per dose cohort, with the potential to add an additional 3 subjects if dose limiting toxicity \[DLT\] is observed at the same dose level at which the toxicity occurred). Enrollment will occur in 2 groups, CA102N monotherapy (Group A) and CA102N combination therapy (Group B).

Subjects will be enrolled in Group A first. Once enrollment in Group A has been completed, subsequent subjects will be enrolled in Group B.

In Part 2 of the study, the safety and tolerability of the preliminary RP2D of CA102N combined with trifluridine/tipiracil (LONSURF) will be further evaluated in up to 12 additional subjects with relapsed or refractory locally advanced or metastatic colorectal cancer who have previously received oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors

Phase 1,Two-part (Dose Escalation, Dose Expansion), Multicenter,Non-randomized,Open-label, Multiple Dose, First-in-human Study of CA102N Monotherapy and of CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors

The exploratory endpoint of the study is to evaluate objective tumor response to CA102N monotherapy and to CA102N in combination with trifluridine/tipiracil (LONSURF) in subjects with locally advanced or metastatic solid tumors and in subjects with locally advanced or metastatic colorectal cancer. The data of tumor response will be collected and evaluated using RECIST version 1.1.

To determine the systemic alteration of COX-2 metabolites affected by CA102N by analyzing urinary COX-2 metabolites, such as PGEM, PGIM and TXBM, using LC-MS/MS.

The primary endpoint for the study is the safety and tolerability of CA102N monotherapy and CA102N combined with trifluridine/tipiracil (LONSURF) as determined according to the NCI-CTCAE version 5.0.

The secondary endpoint of the study is to measure serum concentration of CA102N (ng/mL).

Holy Stone Healthcare Co., Ltd

Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride (with a molar ratio of 1:0.5) was administered at 35 mg/m²/dose orally twice a day, within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period. This treatment cycle was repeated every 4 weeks until treatment withdrawal criteria are met.

The treatment is given in open manner. It was administered until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. If a patient discontinues study treatment for reasons other than radiologic disease progression (e.g., intolerable side effects), the patient was followed for tumour response until radiologic disease progression or initiation of new anticancer therapy (whichever occurs first).

S95005

Vladimir MOISEENKO, Prof.

The purpose of this study is to evaluate the efficacy of S 95005 in patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to standard chemotherapies in terms of Progression-Free Survival rate at 2 months in the Russian population.

Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Failed Standard Chemotherapies

Open-label Multicentre Confirmatory Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Are Refractory or Intolerant to Standard Chemotherapies

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

* submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

percentage of patients alive without investigator-assessed radiological disease progression according to RECIST 1.1 after 2 months

based on Investigator review of the images according to RECIST 1.1

ADIR, a Servier Group company

Institut de Recherches Internationales Servier

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Lonsurf will be administered orally twice a day on days 2-6 and 16-20 of every 28-day cycle at a dose of 25 mg/m2, 20 mg/m2 or 30 mg/m2 depending on cohort assignment.

Lonsurf

Gemcitabine will be intravenously administered on Days 1 and 15 of every 28-day cycle at a dose of 800 mg/m2, 600 mg/m2 or 1000 mg/m2 depending on cohort assignment.

Nab-Paclitaxel will be intravenously administered on Days 1 and 15 of every 28-day cycle at a dose of 100 mg/m2, 75 mg/m2 or 125 mg/m2 depending on cohort assignment.

Nab-Paclitaxel

Patrick J Loehrer, MD

The purpose of this study is to determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel in Pancreatic ductal adenocarcinoma (PDAC)

This is a single-institution, prospective, phase I dose escalation trial of lonsurf combined with gemcitabine and nab-paclitaxel using the 3+3 design. This study will enroll 18 patients over 12-15 months.

Primary Objective To determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel

Secondary Objectives

1. Examine safety and toxicity of the combination
2. Estimate response rate to the combination
3. Estimate median overall survival (mOS) of the treated population
4. Estimate median progression free survival (mPFS) of the treated population
5. Estimate disease control rate (DCR) at 8 weeks
6. Evaluate quality of life while receiving the combination therapy

Initially 3 patients will be enrolled to the starting cohort. If 1 of 3 patients experience a dose-limiting toxicity (DLT) in the first cycle, then an additional 3 evaluable patients will be accrued to that dose level. Dose reductions are not permitted during cycle 1. If 2 or more patients in a cohort experience a DLT, then the previous dose will be considered the recommended phase 2 dose (PR2D) and dose escalation will terminate. Dose escalation will proceed according to the scheme above only after all patients (3 or 6 evaluable patients, depending on the incidence of DLT) have been followed for at least 1 full cycle.

Once dose escalation has been completed, if only 2 dose levels were used to determine the RP2D and depending on how many patients were replaced, additional patients will be enrolled at the RP2D in order to obtain data for 18 patients total.

Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced (PDAC)

Phase I Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

safety and toxicity data will be assessed using NCI CTCAE v5.0

Disease control rate (DCR) as defined by (complete response + partial response + stable disease)

Scale scores were calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

Indiana University

Taiho Oncology, Inc.

Patrick Joseph Loehrer Sr.

Distinguished Professor of Medicine

Immunomodulating Agents

Participants will receive botensilimab at dose 1 given IV and balstilimab given IV.

Participants will receive botensilimab at dose 2 given IV and balstilimab given IV.

Participants will receive botensilimab dose 1 given IV.

Participants will receive botensilimab dose 2 given IV.

Participants will receive select standard of care as determined by the investigator.

An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.

Botensilimab

An anti-programmed death (ligand) 1 \[PD-(L)1\] monoclonal antibody.

Balstilimab

Regorafenib or trifluridine and tipiracil.

Standard of Care

Medical Director

This is an open-label, Phase 2, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetic profiles of botensilimab as monotherapy and in combination with balstilimab or standard-of-care treatments in participants with refractory metastatic colorectal cancer.

This study will enroll adult participants with a confirmed diagnosis of unresectable metastatic colorectal adenocarcinoma (CRC) who have had prior chemotherapy for metastatic or recurrent CRC.

This study will consist of 5 cohorts. In the first and second cohorts, participants will receive 1 of 2 different doses of botensilimab intravenously (IV) and balstilimab IV. In the third and fourth cohorts, participants will receive 1 of 2 different doses of botensilimab. In the fifth cohort, participants will receive standard of care consisting of the investigator's choice of regorafenib or trifluridine and tipiracil.

A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer

A Randomized, Open-Label, Phase 2 Study of Botensilimab (AGEN1181) as Monotherapy and in Combination With Balstilimab (AGEN2034) or Investigator's Choice Standard of Care (Regorafenib or Trifluridine and Tipiracil) for the Treatment of Refractory Metastatic Colorectal Cancer

Objective response rate is defined as the proportion of participants with complete response or partial response, as assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Duration of response is defined as the time from initial objective radiographic response until disease progression or death, whichever occurs first, as assessed using RECIST 1.1.

Progression-free survival is defined as the time from randomization until disease progression or death, whichever occurs first, as assessed using RECIST 1.1.

Overall survival is defined as the time from randomization until death due to any cause.

Agenus Inc.

Symptoms and General Pathology

Neoplasm Metastasis

Liver Neoplasms

Neoplastic Processes

Liver Diseases

Hematinics

Liver Extracts

Combination therapy with Tas-102 and radioembolization using 90Y resin microspheres

Oral nucleoside antitumor agent consisting of α,α,α-trifluorothymidine (FTD) and 5-chloro-6-(2-iminopyrrolidin-1-yl) methyl-2,4 (1H,3H)-pyrimidinedione hydro chloride (TPI) at a molar ratio of 1:0.5.

Tas-102

20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope

SIR-Sphere

Nicholas Fidelman, MD

Katherine Van Loon, MD

This is a phase I dose escalation study (3+3 design) with a dose expansion arm (12 patients) designed to evaluate safety of the combination of Tas-102 and radioembolization using Yttrium-90 (90Y) resin microspheres for patients with chemotherapy-refractory liver-dominant chemotherapy-refractory metastatic colorectal cancer (mCRC).

Randomized studies have demonstrated that Tas-102 has single agent activity against chemotherapy refractory colorectal cancer. A recent pre-clinical study has shown that Tas-102 may have activity as a radiation sensitizer in bladder cancer cell lines. Benefit of single agent Tas-102 against chemotherapy refractory colon cancer and the drug's promise a radiosensitizer make Tas-102 a potential candidate drug for testing in combination with radioembolization using Yttrium-90 resin microspheres in patients with liver-dominant chemotherapy-refractory mCRC. This is a phase I dose escalation study with a dose expansion arm designed to evaluate safety of the combination of Tas-102 and radioembolization using 90Y resin microspheres for patients with chemotherapy-refractory colon or rectal adenocarcinoma metastatic to the liver.

Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Phase I Study of Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Any adverse events grade ≥ 3 will be reviewed by the treating interventional radiologist and medical oncologist within 24 hours of being informed event. If none of the 3 patients in a cohort experiences a DLT, another 3 patients will be treated at the next higher dose level. However, if 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level. The dose escalation will continue until at least 2 patients among a cohort of 3-6 patients experience DLTs (i.e., ≥ 33% of patients with a dose-limiting toxicity at that dose level) or until 3-6 patients had been treated at TAS-102 dose of 35mg/m2 per day in 2 divided doses (up to a maximum of 80 mg per dose) administered concurrently with radioembolization cycles 1 and 2 without experiencing a DLT. DLT window will be 56 days (cycle 1, day 1 to cycle 2, day 28). Dose limiting toxicity will be reached when one of the clinical and/or laboratory parameters are met

Traditional 3+3 design will be used to determine the recommended dose for the dose expansion phase will be defined as the dose level just below this toxic dose level.

Radiographic overall response rate (measured in accordance to Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) using imaging. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in the sum of the longest diameter of target lesionsStable Disease (SD): Small changes that do not meet the criteria for CR, PR, or Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions. ORR will be defined as a ratio of the number of patients who demonstrated complete response (CR) or partial response (PR) to the number of all evaluated patients.

PFS will be defined as a time period that started at enrollment, during which a patient neither progressed nor died based on radiographic response.

HPFS will be defined as a time period that started at enrollment, during which a patient neither progressed in the liver nor died based on radiographic response.

EHPFS will be defined as a time period that started at enrollment, during which a patient neither progressed outside the liver nor died based on radiographic response

Overall Survival will be analyzed 12 months after the last patient is enrolled. Overall survival will be assessed using a two-sided, log-rank test. The survival function will be estimated using the Kaplan-Meier product limit method. In addition, two-sided 95% confidence intervals for the median overall survival will be computed

Proportion of patients with carcinoembryonic antigen (CEA) response with ≥ 50% decline from baseline (in patients with baseline level ≥ 3.2) post combination therapy with Tas-102 and 90Y radioembolization. Maximum percent change will be calculated. CEA level will only be followed for participants with elevated level (≥3.2) at baseline.

Sirtex Medical

Taiho Pharmaceutical Co., Ltd.

University of California, San Francisco

Nivolumab

Relatlimab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Nivolumab-relatlimab FDC

Regorafenib

Bristol-Myers Squibb

The purpose of this study is to evaluate relatlimab in combination with nivolumab, administered as a fixed-dose combination (nivolumab-relatlimab FDC, also referred to as BMS-986213) for the treatment of non-microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC) participants who failed at least 1 but no more than 4 prior lines of therapy for metastatic disease.

A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer

A Phase 3, Randomized, Open-label Study of Relatlimab-nivolumab Fixed-dose Combination Versus Regorafenib or Trifluridine + Tipiracil (TAS-102) for Participants With Later-lines of Metastatic Colorectal Cancer

The EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire-Core 30 (QLQ-C30) consists of 30 questions incorporated into 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, pain, nausea and vomiting), a global health status / Quality of Life scale, and six single symptom items. All of the scale and single-item measures range in score from 0 to 100, where a higher score represents a higher response level. High functional scores indicates more favorable outcomes and a higher score on the symptom domains indicates higher symptom burden/less favorable patient outcome.

QoL = Quality of Life. The EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire-Core 30 (QLQ-C30) consists of 30 questions incorporated into 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, pain, nausea and vomiting), a global health status / Quality of Life scale, and six single symptom items. All of the scale and single-item measures range in score from 0 to 100, where a higher score represents a higher response level. High functional scores indicates more favorable outcomes and a higher score on the symptom domains indicates higher symptom burden/less favorable patient outcome.

Irinotecan

Lenograstim

Mitogens

Guadecitabine

Azacitidine

Topoisomerase I Inhibitors

Enzyme Inhibitors

Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.

Various doses of SGI-110 are tested to determine the maximum tolerated dose in combination with irinotecan.

Subjects receive SGI-110 on days 1-5 and irinotecan on days 8 and 15 of each 28-day cycle.

Growth factor support (filgrastim and peg-filgrastim) is given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.

Subjects received either regorafenib or TAS-102 based on physician and patient preference. Subjects that had received one of these standard of care drugs (regorafenib or TAS-102) prior to enrollment received the other on study.

Regorafenib taken daily from days 1-21 of each 28-day cycle or TAS-102 taken twice daily on days 1-5 and 8-12 of each 28-day cycle.

Subjects who had disease progression on Arm B were given the option to receive Arm A study drugs after a 14 day wash-out period.

* Dose level 1 (DL1): 45 mg/m\^2 administered as a subcutaneous injection
* Dose level 1G (DL1G): 45 mg/m\^2 administered as a subcutaneous injection + growth factor support
* Dose level -1 (DL-1): 30 mg/m\^2 administered as a subcutaneous injection
* Dose level -1G (DL-1G): 30 mg/m\^2 administered as a subcutaneous injection + growth factor support

SGI-110 Dose Escalation

45 mg/m\^2 administered as a subcutaneous injection

SGI-110

Nilo Azad, MD

This is a phase I/II study of the combination of Guadecitabine (SGI-110) and previously treated metastatic colorectal cancer patients. This study will be conducted in two components. First, patients will be enrolled in a phase I study of SGI-110 combined with irinotecan in a standard 3+3 design. After the maximum tolerated dose (MTD) is determined, patients will subsequently be enrolled in a 2:1 randomized phase II study of SGI-110 and irinotecan versus the standard of care regorafenib or Lonsurf (TAS-102).

In Phase 2, Arm B patients who have disease progression will be given the option to receive Arm A study drugs.

Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer

A Phase I Study of SGI-110 Combined With Irinotecan Followed by a Randomized Phase II Study of SGI-110 Combined With Irinotecan Versus Regorafenib or TAS-102 in Previously Treated Metastatic Colorectal Cancer Patients

Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study:

1. grade 4 thrombocytopenia lasting \>7days
2. any grade 3-4 febrile neutropenia
3. grade 3 or higher non-hematologic toxicity unless it could be managed by supportive treatment
4. any other clinically significant adverse event which would place subjects at undue safety risk, or results in discontinuation of treatment.

Progression Free Survival is the time (in months) from start of treatment to progression, clinical deterioration attributed to disease, or death.

Overall Survival is defined as the time (in months) between the start of treatment and death.

Objective Response Rate (ORR) is defined as the number of subjects achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. CR = disappearance of all target lesions, PR = at least 30% decrease in the sum of diameters of target lesions.

Van Andel Research Institute

Astex Pharmaceuticals, Inc.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

18 patients from Arm B were eligible to "crossover" to receive Arm A study treatment after they had progression with Arm B treatment. They were assessed for adverse events after receiving Arm A treatment. Their adverse events are reported here in a separate arm.

Guadecitabine (SGI-110) 45 mg/m\^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m\^2 was administered IV on days 8 and 15 of each 28-day cycle.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sym004 Versus TAS-102 in Patients With mCRC	NCT03717038	Metastatic Colo... Colorectal Canc... Carcinoma	Sym004 TAS-102	18 Years -	Symphogen A/S
First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors	NCT03616574	Advanced or Met... Advanced or Met...	CA102N LONSURF	18 Years -	Holy Stone Healthcare Co., Ltd
First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors	NCT03616574	Advanced or Met... Advanced or Met...	CA102N LONSURF	18 Years -	Holy Stone Healthcare Co., Ltd
Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Failed Standard Chemotherapies	NCT03274882	Metastatic Colo...	S95005	18 Years -	Servier
Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced (PDAC)	NCT04046887	Pancreatic Canc... Pancreatic Duct...	Lonsurf Gemcitabine Nab-Paclitaxel	18 Years -	Indiana University
Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced (PDAC)	NCT04046887	Pancreatic Canc... Pancreatic Duct...	Lonsurf Gemcitabine Nab-Paclitaxel	18 Years -	Indiana University
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer	NCT05608044	Metastatic Colo...	Botensilimab Balstilimab Standard of Car...	18 Years -	Agenus Inc.
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer	NCT05608044	Metastatic Colo...	Botensilimab Balstilimab Standard of Car...	18 Years -	Agenus Inc.
Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases	NCT02602327	Colon Cancer Rectal Cancer Liver Metastase...	Tas-102 SIR-Sphere	18 Years -	University of California, San Francisco
A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer	NCT05328908	Colorectal Neop...	Nivolumab-relat... Regorafenib TAS-102	18 Years -	Bristol-Myers Squibb
Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer	NCT01896856	Previously Trea...	SGI-110 Dose Es... Regorafenib TAS-102 SGI-110 Irinotecan	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for lonsurf

Every month we try and update this database with for lonsurf 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 lonsurf

Every month we try and update this database with for lonsurf 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 lonsurf 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.