Triplet Combination of Cytotoxics as First-line Treatment for Metastatic Gastric Cancer

Phase 3

Recruiting

• Conditions: Metastatic Gastric Cancer
• Interventions: Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-fluorouracil

• Registration Number: NCT04358354
• Lead Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Brief Summary

This parallel, randomized, open-label study will evaluate the effect on overall survival of irinotecan on oxaliplatin and 5-fluorouracil (5-FU) in patients with HER2-negative and pMMR metastatic gastric cancer. Irinotecan will be administered as intravenous infusion of 150 mg/m2 every 2 weeks. Oxaliplatin will be given 85 mg/m2 and 5-FU will be given 400mg/m2 iv and 2400mg/m2 civ 48 hours fortnightly. Treatment will continue until disease progress or untolerable toxicity appears. The target sample size is 350-400 patients.

Detailed Description

Eligible patients will be randomly assigned to FOLFOXiri group and FOLFOX group. Stratification factors include ECOG PS, disease extent and pathological subtypes. Efficacy will be evaluated every 3-4 cycles with RECIST. Toxicity will be assessed with WHO CTC 3.0 every 2 weeks.

Study Timeline

• Study First Submitted: 2020-04-11
• Study First Submitted QC: 2020-04-20
• Study First Posted: 2020-04-24
• Study Start: 2020-10-22
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-13
• Last Update Posted: 2021-07-19
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 388

Inclusion Criteria

1. Age 18-75 years old, gender is not limited;
2. Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or gastro-esophageal junction;
3. Pathologically confirmed adenocarcinoma;
4. Expected survival time ≥ 3 months;
5. ECOG PS 0-3;
6. Adequate bone marrow function reserve: white blood cell count ≥ 3.0 × 10*9 / L, neutrophil count ≥ 1.5 × 10*9/ L; platelet count ≥ 100 ×10*9/ L; hemoglobin ≥ 90 g / L;
7. AST and ALT ≤ 2.5 times the upper limit of normal value, total bilirubin ≤ 2 times the upper limit of normal value; serum creatinine ≤ 1.5 times the upper limit of normal value;
8. Be able to understand the research process, volunteer to participate in the study, and sign an informed consent form.

Exclusion Criteria

1. Patients known to be allergic to active or other components of chemotherapeutic drugs;
2. Patients with severe peritoneal dissemination and GI obstruction;
3. Her-2 overexprssion or d-MMR;
4. Severe or uncontrolled infections that may affect the evaluation of the study treatment or study results;
5. History of other malignant tumors in the past 5 years (except for cured cervical carcinoma in situ or basal cell carcinoma of the skin);
6. Participated in other clinical trials within 4 weeks prior to the start of the study;
7. Pregnant or lactating women, or women of childbearing age who refuse to take effective contraception during the study period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFOXiri group	Irinotecan	Irinotecan 150 mg/m2 iv drip d1; Oxaliplatin 85 mg/m2 iv drip d1; LV 200 mg/m2 iv drip d1; 5FU 400mg/m2 iv bolus and 2400 mg/m2 civ; The regimen will be repeated every 2 weeks until disease progression or untolerable toxicity.
FOLFOXiri group	Oxaliplatin	Irinotecan 150 mg/m2 iv drip d1; Oxaliplatin 85 mg/m2 iv drip d1; LV 200 mg/m2 iv drip d1; 5FU 400mg/m2 iv bolus and 2400 mg/m2 civ; The regimen will be repeated every 2 weeks until disease progression or untolerable toxicity.
FOLFOXiri group	5-fluorouracil	Irinotecan 150 mg/m2 iv drip d1; Oxaliplatin 85 mg/m2 iv drip d1; LV 200 mg/m2 iv drip d1; 5FU 400mg/m2 iv bolus and 2400 mg/m2 civ; The regimen will be repeated every 2 weeks until disease progression or untolerable toxicity.
FOLFOX group	5-fluorouracil	Oxaliplatin: 85 mg/m2 iv drip d1; LV 200 mg/m2 iv drip d1; 5FU 400mg/m2 iv bolus and 2400 mg/m2 civ 46h; The regimen will be repeated every 2 weeks until disease progression or untolerable toxicity.
FOLFOX group	Oxaliplatin	Oxaliplatin: 85 mg/m2 iv drip d1; LV 200 mg/m2 iv drip d1; 5FU 400mg/m2 iv bolus and 2400 mg/m2 civ 46h; The regimen will be repeated every 2 weeks until disease progression or untolerable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	2 years	OS is defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log or the date of last follow-up.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	1 year	PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)	24 weeks	For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels.
Duration of Response	1 year	Duration of response was defined for responders as the time from the date on which the CR or PR was first recorded to the date on which PD is first noted. Participants were censored on the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.
European Organisation For the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C-30) Questionnaire Scores	2 years	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score equals (=) better level of functioning or greater degree of symptoms.
EORTC Quality of Life Questionnaire-Stomach Cancer Specific (QLQ STO22) Questionnaire Scores	2 years	The QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
Treatment associated toxicities	2 years	WHO CTC 3.0

Trial Locations

Locations (1)

The Sixth Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China