Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Aflibercept

Oxaliplatin

Folic Acid

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients in the 5-FU / oxaliplatin arm receive modified (m) FOLFOX 7: Folinic acid 350 mg/m² and oxaliplatin 68 mg/m² by concurrent 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion every 2 weeks (qd15).

This regimen represents the 80% dosage reduced mFOLFOX 7. The 80% dose reduction was shown to be a tolerable regimen in frail elderly patients in the FOCUS 2 study.

Patients in the 5-FU / aflibercept arm receive aflibercept 4mg/kg as 1-h infusion followed by folinic acid 350 mg/m² by 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion (mLV5FU2) every 2 weeks (qd15).

The decision to use reduced doses of 5-FU and folinic acid was made to have comparable doses to the reduced FOLFOX 7.

Patients receive aflibercept 4mg/kg as 1-h infusion followed by folinic acid 350 mg/m² by 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion (mLV5FU2) every 2 weeks (qd15).

Aflibercept + mLV5FU2

Patients in this arm receive modified (m) FOLFOX 7: Folinic acid 350 mg/m² and oxaliplatin 68 mg/m² by concurrent 2-h intravenous infusion, 5-FU 1920 mg/m² 46-h intravenous infusion every 2 weeks (qd15).

mFOLFOX7

Salah-Eddin Al-Batran, Prof. Dr.

This is a controlled, open-label, randomized phase- II trial (1:1 randomization) investigating 5-FU + aflibercept and 5-FU + oxaliplatin in elderly and frail elderly patients with mCRC scheduled to receive first line treatment.

The current trial seeks to evaluate a new treatment option for elderly / frail elderly patients with mCRC including 5-FU - better tolerated than capecitabine in the FOCUS2 study - in conjunction with aflibercept, a broad active anti-angiogenic drug within a randomized phase-II setting. Patients will be randomized using a 1:1 randomization between 5-FU / aflibercept and 5-FU / oxaliplatin using the oxaliplatin-based regimen established in FOCUS2 trial. Main goal is to estimate the 6-months PFS rate with 5-FU / Aflibercept and the safety of this regimen. The decision to use a randomized phase-II design using the "FOCUS2- FOLFOX" is based on two assumptions; (i) Bias can be better controlled by using a randomized phase-II design (ii) A clear standard regimen in frail elderly cannot be defined, but FOLFOX was superior to 5-FU alone in FOCUS2 and the patient population included in the FOCUS2 study represents the patient population scheduled to be included in the current trial.

Provided the randomized phase-II study shows adequate efficacy of 5-FU / aflibercept and a tolerable safety profile, the study will be carried on to the phase-III part of the trial. Description of the terms and conditions to expand the current trial are not part of this protocol. Briefly, a potential phase-III study should aim at showing non-inferiority of 5-FU / aflibercept regarding 6-months PFS rate as primary endpoint. This would allow to include all patients from the phase-II part in the phase-III study in order to save time and patients.

Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer

Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Metastatic Colorectal Cancer

As calculated over the whole treatment duration and summarized descriptively by summary statistics.

AE's will be summarized by presenting the number and percentages of patients having any AE

Dose modifications, including discontinuations, will be summarized by presenting the number and percentages of patients having any dose modification

Rate of treatment discontinuations during the study

Summary of lab abnormalities as assessed in the documentation

Quality of life (QoL) as measured by EQ-5D-5L at d1 of each cycle and on EOT.

Geriatric assessment as measured by using G8, ADL and IADL

Overall treatment utility is evaluated according to the principles used in the FOCUS2 trial. Cf. Seymour et al. Geriatric oncol 2013.

STABIL - Statistische und Biometrische Lösungen

Trium Analysis Online GmbH

Sanofi

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Rare Diseases

Stomach Neoplasms

Esophageal Neoplasms

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

Trastuzumab

Pembrolizumab

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* CA4948 (dose will depend on dose level assigned) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days.
* Each cycle is 14 days.

* CA4948 (dose will be the recommended phase II dose found in the dose escalation portion of study) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days.
* Each cycle is 14 days.

* CA4948 (dose will be the recommended dose found in the dose escalation portion of study) twice daily by mouth Standard of care mFOLFOX7 every 14 days. Pembrolizumab on day 1 of every 3 cycles. Trastuzumab every 14 days.
* Each cycle is 14 days.

CA-4948

400 mg IV on Day 1 of every 3 cycles (C1D1, C4D1, C7D1,...) and dosing may continue for a max of 2 years

6 mg/kg IV loading dose on Cycle 1 Day 1 and 4 mg/kg IV on Day 1 of every subsequent cycle

Patrick Grierson, M.D., Ph.D.

Olivia Aranha, M.D., Ph.D.

Matthew Ciorba, M.D.

Kian-Huat Lim, M.D., Ph.D.

Michael Iglesia, M.D., Ph.D.

Katrina Pedersen, M.D.

Rama Suresh, M.D.

Benjamin Tan, M.D.

Nikolaos Trikalinos, M.D.

David DeNardo, Ph.D.

Feng Gao, Ph.D.

This is a phase I trial of CA-4948 in combination with FOLFOX/PD-1 inhibitor with or without trastuzumab for unresectable gastric, GEJ, and esophageal cancer. During the Dose Escalation portion of the study, different dose levels of CA-4948 in combination with FOLFOX/nivolumab will be evaluated by BOIN algorithm.

Dose Expansion will include Cohorts A and B. Expansion Cohort A will enroll up to 12 patients with HER2 negative gastric, GEJ, and esophageal cancer at the expansion dose of CA-4948 determined during Dose Escalation and will use the same treatment regimen of FOLFOX/nivolumab. Expansion Cohort B will investigate CA-4948 at the dose determined during Dose Escalation in combination with FOLFOX/pembrolizumab and trastuzumab in up to 12 patients with HER2 positive disease; however, the initial 6 patients will be considered safety lead-in to confirm the safety and tolerability of this combination; if determined to be safe, an additional 6 patients will be enrolled for a total of 12 in Cohort B.

The dose escalation phase will occur first. In the dose expansion phase, participants will be assigned to either Cohort A or Cohort B and treated in parallel.

CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer

Phase I Trial of CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer

* Proportion of participants with no disease progression
* Progressive disease (PD): At least a 20% increase in the sum of the 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. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

* Proportion of participants who had complete response, partial response, or stable disease by RECIST 1.1 Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
* Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

* Defined as number of participants with complete response or partial response per RECIST 1.1 guidelines.
* Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
* Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

-Defined as number of participants with complete response or partial response per iRECIST guidelines.

* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. The alive patients without progression are censored at the date of last follow-up.
* Progressive disease (PD): At least a 20% increase in the sum of the 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. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

-OS is defined as the duration of time from start of treatment to time of death from any cause. The alive patients are censored at the date of last follow-up.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer	NCT03530267	Colorectal Canc...	Aflibercept + m... mFOLFOX7	70 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer	NCT03530267	Colorectal Canc...	Aflibercept + m... mFOLFOX7	70 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer	NCT05187182	Gastric Cancer Esophageal Canc... Stomach Cancer Esophagus Cance... Gastroesophagea...	CA-4948 Nivolumab Pembrolizumab Trastuzumab mFOLFOX7	18 Years -	Washington University School of Medicine
Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer	NCT03530267	Colorectal Canc...	Aflibercept + m... mFOLFOX7	70 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Spots Global Cancer Trial Database for mfolfox7

Every month we try and update this database with for mfolfox7 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 mfolfox7

Every month we try and update this database with for mfolfox7 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 mfolfox7 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.