Docetaxel, Oxaliplatin and 5-FU for Gastric Cancer With Inoperable Malignant Bowel Obstruction

Study Overview
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Brief Summary
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This is a multi-center, non-randomized, 3-cohort, phase II trial, evaluating a triplet combination of docetaxel, oxaliplatin and fluorouracil for gastric cancer with peritoneal carcinomatosis and inoperable malignant bowel obstruction.

Detailed Description
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The primary study hypothesis is that the regimen will provide a clinically meaningful bowel obstruction clearance. This trial has 3 paralleled cohorts with the same experimental regimen: Cohort A (first-line therapy) will include 35 participants who have not received any palliative chemotherapy; Cohort B (second-line therapy) will include 22 participants who progress after the first-line therapy; Cohort C (third- or later-line therapy) plans to include 22 cases who have received two or more prior therapies for their metastatic disease.

Official Title
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A Multi-center, Non-randomized, Three-cohort, Phase II Trial of a Modified Triplet Combination of Docetaxel, Oxaliplatin and Fluorouracil for Gastric Cancer With Peritoneal Carcinomatosis and Inoperable Malignant Bowel Obstruction

Conditions
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Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Peritoneal Carcinomatosis

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Oxaliplatin
* Drug: Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years of age; ECOG PS ≤3; pathologically diagnosed gastric or gastroesophageal junctional adenocarcinoma; peritoneal carcinomatosis established by imaging data or pathological evidence; MBO below the Treitz ligament based on clinical grounds or radiological findings; considered as inoperable MBO by two independent surgical consultants; Hb≥60g/L, WBC ≥4×10E9/L, ANC≥2×10E9/L，PLT≥100×10E9/L; Cr≤ Upper Normal Limit(UNL); Tbil≤1.5 UNL,AST≤1.5 UNL, ALT≤1.5 UNL, ALP≤1.5 UNL; Written informed consent form paticipants. Exclusion Criteria: treated by a combination regimen containing all the study drugs; allergy to any of the study drugs; HER-2 amplification or overexpression, mismatch repair protein expression deletion (dMMR), or genetic testing suggestive of high microsatellite instability (MSI-H); strangulated intestinal obstruction; active gastrointestinal bleeding; uncontrolled active infection; unstable heart diseases with severe ECG abnormalities or affect clinical treatment (such as cardiac insufficiency, myocardial infarction, angina); severe lung diseases (such as interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc); mental disorders that affect clinical treatment or central nervous system diseases; concomitant cerebral parenchymal or meningeal metastasis; HIV infection or untreated active hepatitis; bowel surgery or stenting required due to obstruction; pregnant or lactating women; other conditions that are not suitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (First-Line Therapy)<br>Docetaxel 25 mg/square metre, ivdrip 60 min, D1, D8, D15; Oxaliplatin 85 mg/square metre, ivdrip 180 min, D1, D15; 5Fu 1200 mg/square metre, civ 24 hours, D1, D8, D15; Repeat every 4 weeks. | Drug: Docetaxel<br>* 25 mg/square metre, D1, D8, D15, repeat every 4 weeks.<br>Drug: Oxaliplatin<br>* 85 mg/msquare metre, D1, D15, repeat every 4 weeks.<br>Drug: Fluorouracil<br>* 1200 mg/square metre, D1, D8, D15, repeat every 4 weeks.<br>* Other names: 5-FU;|
| Experimental: B (Second-Line Therapy)<br>Docetaxel 25 mg/square metre, ivdrip 60 min, D1, D8, D15; Oxaliplatin 85 mg/square metre, ivdrip 180 min, D1, D15; 5Fu 1200 mg/square metre, civ 24 hours, D1, D8, D15; Repeat every 4 weeks. | Drug: Docetaxel<br>* 25 mg/square metre, D1, D8, D15, repeat every 4 weeks.<br>Drug: Oxaliplatin<br>* 85 mg/msquare metre, D1, D15, repeat every 4 weeks.<br>Drug: Fluorouracil<br>* 1200 mg/square metre, D1, D8, D15, repeat every 4 weeks.<br>* Other names: 5-FU;|
| Experimental: C (Third- or Later-Line Therapy)<br>Docetaxel 25 mg/square metre, ivdrip 60 min, D1, D8, D15; Oxaliplatin 85 mg/square metre, ivdrip 180 min, D1, D15; 5Fu 1200 mg/square metre, civ 24 hours, D1, D8, D15; Repeat every 4 weeks. | Drug: Docetaxel<br>* 25 mg/square metre, D1, D8, D15, repeat every 4 weeks.<br>Drug: Oxaliplatin<br>* 85 mg/msquare metre, D1, D15, repeat every 4 weeks.<br>Drug: Fluorouracil<br>* 1200 mg/square metre, D1, D8, D15, repeat every 4 weeks.<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 60-day Obstruction Clearance Rate | proportion of participants who achieved obstruction clearance within 60 days from start of treatment | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day Obstruction Clearance Rate | proportion of participants who achieved obstruction clearance within 30 days from start of treatment | 30 days | 
| Time to Obstruction Clearance | interval from start of treatment to obstruction clearance | 60 days | 
| Obstruction Clearance Duration | interval from obstruction clearance to the next malignant bowel obstruction | 2 years | 
| Safety in terms of Adverse Events | according to Common Terminology Criteria for Adverse Events version 5.0 | 2 years | 
| Overall Survival | interval from start of treatment to death or last follow-up | 2 years | 
| Quality of Life assessed by EORTC QLQ-OG25 | in terms of European Organization for Research and Treatment of Cancer Quality of Life questionnair OG25 | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant Bowel Obstruction, Docetaxel, Oxaliplatin, Fluorouracil