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

Analgesics

Hematinics

Vitamins

Irinotecan

Molgramostim

Sargramostim

Leucovorin

Fluorouracil

Levoleucovorin

Immunomodulating Agents

Oxaliplatin

Interleukin-2

Iron-Dextran Complex

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Analgesics, Non-Narcotic

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

The FOLFOXIGIL chemoimmunotherapy regimen is composed by FOLFOXIRI chemotherapy and the immunotherapy of GM-CSF and IL-2.

FOLFOXIRI: Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + Levoleucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1, repeated every 2 weeks.

GM-CSF 150ug s.c. d3-7; Interleukin-2 100MIU s.c. d8-14 and d17-d28, Repeated every 4 weeks.

Treatment will be administered until progression, patients' withdrawal of consent, unacceptable toxicity.

Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + Levoleucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1, Repeated every 2 weeks.

Treatment will be administered until progression, patients' withdrawal of consent, unacceptable toxicity.

Levoleucovorin 200 mg/m² 2-hours IV day 1

5-FU 2800 mg/m² 46-hours flat continuous infusion IV

5-FU

GM-CSF 150ug s.c. d3-7 , Repeated every 4 weeks.

GM-CSF

Interleukin-2 100MIU s.c. d8-14 and d17-d28, Repeated every 4 weeks.

IL-2

Rongbo Lin, MD

A randomized phase II trial of FOLFOXIRI in Combination With GM-CSF and IL-2 (FOLFOXIGIL) Versus FOLFOXIRI as First-line Treatment for Patients With Metastatic Colorectal Cancer.

The triple drug regimen FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) for the first-line treatment of metastatic colorectal cancer has shown a significant increase in response rate and overall survival compared to FOLFIRI and FOLFOX. The combination of GOLF chemotherapy with GM-CSF and IL-2（GOLFIG regimen） has shown more active than the standard FOLFOX chemotherapy in first-line mCRC patients，through the chemoimmunomodulatory effects. SO the FOLFOXIGIL chemoimmunotherapy regimen was designed with the same principle to evaluate the antitumor frontline efficacy in comparison with the FOLFOXIRI regimen as first-line treatment of mCRC patients. This is a multicenter, randomized controlled, double-blind, phase II trial.

Phase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC

FOLFOXIRI in Combination With GM-CSF and IL-2 (FOLFOXIGIL) Versus FOLFOXIRI as First-line Treatment for Patients With Metastatic Colorectal Cancer: a Phase II Trial by the FNF Team.

PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of randomization to the date of first documented progression disease (PD) , or death from any cause.

PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.

CR + PR rate according to the RECIST version 1.1 guidelines.

Toxicity assessed using the NCI common toxicity criteria, version 4.01

OS was calculated from the date of randomization to death from any cause.

PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause.

Scores according to EORTC QLQ-C30 scoring manual

Fujian Cancer Hospital

Symptoms and General Pathology

Rare Diseases

Esophageal Neoplasms

Death

Carcinoma

Adenocarcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Pharmaceutical Solutions

Bone Density Conservation Agents

Pembrolizumab

Cisplatin

Calcium

Calcium, Dietary

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Hormones

Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either:

* FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR
* FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle.

All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year.

Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either:

* FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR
* FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle.

All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year.

pembrolizumab

placebo

cisplatin

radiotherapy

leucovorin

levoleucovorin

oxaliplatin

Medical Director

The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in:

* participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10
* participants whose tumors express PD-L1 CPS ≥1
* all participants

The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to:

* EFS in participants whose tumors express PD-L1 CPS ≥10
* EFS in participants whose tumors express PD-L1 CPS ≥1
* EFS in all participants
* OS in participants whose tumors express PD-L1 CPS ≥10
* OS in participants whose tumors express PD-L1 CPS ≥1
* OS in all participants

Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either:

* FP (5-fluorouracil \[5-FU\] + cisplatin) or
* FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).

Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)

A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

EFS is defined as the time from randomization to an event defined as local, regional, or distant radiological recurrence as assessed by the investigator; clinical recurrence as assessed by the investigator with histopathologic confirmation (in the absence of radiological disease recurrence by investigator assessment); or death from any cause, whichever occurs first.

OS is defined as the time from randomization to death from any cause.

An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Merck Sharp & Dohme LLC

Trastuzumab

Tucatinib

Bevacizumab

Cetuximab

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab

300mg given by mouth (orally) twice daily

tucatinib

8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.

trastuzumab

bevacizumab

400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

cetuximab

85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC	NCT03222089	Metastatic Colo...	Irinotecan Oxaliplatin Levoleucovorin 5-FU GM-CSF IL-2	18 Years - 75 Years	Fujian Cancer Hospital
Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)	NCT04210115	Esophageal Squa... Gastroesophagea... Esophageal Aden...	pembrolizumab placebo cisplatin 5-FU radiotherapy leucovorin levoleucovorin oxaliplatin	18 Years -	Merck Sharp & Dohme LLC
Phase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC	NCT03222089	Metastatic Colo...	Irinotecan Oxaliplatin Levoleucovorin 5-FU GM-CSF IL-2	18 Years - 75 Years	Fujian Cancer Hospital
A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer	NCT05253651	Colorectal Neop...	tucatinib trastuzumab bevacizumab cetuximab oxaliplatin leucovorin levoleucovorin fluorouracil	18 Years -	Seagen Inc.
Phase 2 Futibatinib in Combination With PD-1 Antibody Based Standard of Care in Solid Tumors	NCT05945823	Locally Advance... Esophageal Aden... Esophageal Squa... Siewert Type 1 ... Pancreatic Canc...	Futibatinib Pembrolizumab Cisplatin 5-FU Oxaliplatin Leucovorin Levoleucovorin Irinotecan	18 Years -	Taiho Oncology, Inc.
Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014)	NCT04949256	Metastatic Esop...	Pembrolizumab Lenvatinib Cisplatin 5-FU Oxaliplatin Leucovorin Levoleucovorin Paclitaxel	18 Years -	Merck Sharp & Dohme LLC
Treatment of Colorectal Liver Metastases With Immunotherapy and Bevacizumab	NCT03698461	Colorectal Neop... Neoplasm Metast... Colonic Neoplas... Rectal Neoplasm...	Atezolizumab Bevacizumab Oxaliplatin Levoleucovorin 5-FU	20 Years -	Asan Medical Center
Treatment of Colorectal Liver Metastases With Immunotherapy and Bevacizumab	NCT03698461	Colorectal Neop... Neoplasm Metast... Colonic Neoplas... Rectal Neoplasm...	Atezolizumab Bevacizumab Oxaliplatin Levoleucovorin 5-FU	20 Years -	Asan Medical Center

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