Chemotherapy for Patients With Cancer of the Stomach

Phase 1

Completed

• Conditions: First-line Treatment for Patients With Non-resectable Gastric Cancer or Cancer of the Esophagus or
• Interventions: Drug: DOS3w Dose level 1B; Drug: DOS2w Dose level 2A; Drug: DOS2w Dose level 3A; Drug: DOS2w Dose level 4A; Drug: DOS2w Dose level 1A; Drug: DOS3w Dose level 2B; Drug: DOS3w Dose level 3B

• Registration Number: NCT01928524
• Lead Sponsor: Per Pfeiffer

Brief Summary

The purpose of this study is to determine maximal tolerable dose (MTD) of the combination of docetaxel, oxaliplatin and S1 (DOS) to patients with gastric cancer.

Detailed Description

The primary aim of this dose-finding study is to determine the maximum tolerated doses of docetaxel, oxaliplatin and S1 given every second (DOS2w) or third (DOS3w) week as first-line treatment in patients with advanced gastro-esophageal cancer. Secondary end points are to evaluate toxicities according to NCI-CTCAE v. 4, response rate, progression-free survival and overall survival

Primary Outcome Measure:

To determine maximum tolerated dose (MTD) for the the combination regimes (DOS2w) and (DOS3w).

The investigators have planned to examine 4 dose levels of (DOS2w) and 3 dose levels of (DOS3w).

Methods:

This dose-finding study is planned to include a total of 24 patients with advanced gastro-esophageal cancer, adenocarcinoma.

12 patients will be included in (DOS2w) at four at progressively higher dose levels.

Chemotherapy will be repeated day 1 every second week to a maximum of nine courses.

12 patients will be included in (DOS3w) at three progressively higher dose levels.

Chemotherapy will be repeated day 1 every third week to a maximum of six courses.

In both (DOS2w) and (DOS3w) dose-limiting toxicity (DLT) will be evaluated after the first course. In case of DLT among one of the three patients during the first course of treatment additional three patients will be added at the respective dose level. Dose escalation is continues if 0/3 or 1/6 patients experience DLT.

Patients will be evaluated with a ct-scan at baseline and after every three or four cycles to exclude progression and evaluate response. Response is assessed by the investigator according to RECIST version 1.1.

Study Timeline

• Study First Submitted: 2013-08-21
• Study First Submitted QC: 2013-08-21
• Study First Posted: 2013-08-26
• Study Start: 2013-09
• Primary Completion: 2015-06-05
• Study Completion: 2015-12-17
• Results First Submitted: 2020-10-29
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-28
• Last Update Submitted: 2021-01-28
• Results First Posted: 2021-02-16
• Last Update Posted: 2021-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

1. Histological proven adenocarcinoma of the esophagus or the ventricle (ECV), and which cannot be treated curatively.
2. Age ≥ 18 years.
3. WHO performance status 0-1.
4. Neutrophils ≥ 1,5 x 109/L and platelets ≥ 100 x 109/L.
5. Bilirubin ≤ 1,5 x UNL (Upper Normal Limit) and ASAT and/or ALAT ≤ 3 x UNL.
6. Creatinine-clearance ≥ 60 ml/min.
7. Planned first day of treatment within 8 days after inclusion in the study.
8. Signed consent form.

Exclusion Criteria

1. No previous treatment with chemotherapy, except for (neo)-adjuvant chemotherapy for adenocarcinoma - treatment should have been completed at least 6 months before entrance in this study.
2. No sensory neuropathy.
3. No previously treatment with docetaxel, oxaliplatin or S1.
4. No clinical suspicion of brain metastases.
5. No cytotoxic treatment or other experimental treatment within 2 weeks of inclusion in the study.
6. Other serious disease (i.e. heart disease, AMI within 1 year or ongoing infection).
7. No pregnant women or women who are lactating. Patients who are not using contraception.
8. No known DPD-deficiency or known allergy to taxanes or platinum.
9. No signs of physical or mental illness that would prevent absorption of oral treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DOS3W Dose level 1B	DOS3w Dose level 1B	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 3 weeks.
DOS2W Dose level 2A	DOS2w Dose level 2A	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks.
DOS2W Dose level 3A	DOS2w Dose level 3A	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks.
DOS2W Dose level 4A	DOS2w Dose level 4A	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks.
DOS2W Dose level 1A	DOS2w Dose level 1A	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks.
DOS3W Dose level 2B	DOS3w Dose level 2B	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 3 weeks.
DOS3W Dose level 3B	DOS3w Dose level 3B	Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 3 weeks.

Primary Outcome Measures

Name	Time	Method
Median Overall Survival	Up to 2 years after first administration of DOS

Trial Locations

Locations (1)

Odense University Hospital; 🇩🇰 Odense, Denmark