Docetaxel and Oxaliplatin in Gastric Cancer

A Randomized Phase II Study of Docetaxel in Combination With Oxaliplatin With or Without 5-FU or Capecitabine in Metastatic or Locally Recurrent Gastric Cancer Previously Untreated With Chemotherapy for Advanced Disease

This phase II study addressed the use of docetaxel in combination with oxaliplatin with or without 5-FU or capecitabine in metastatic or locally recurrent gastric cancer previously untreated with chemotherapy for advanced disease. Prior to this study a pilot phase I (part I) determined the optimal dose by assessing the safety and tolerability of 2 dose levels in each arm. The optimal dose was administered in the Part II study. Participants who received the optimal dose in each treatment arm in Part I were included in the Part II analysis population.

Primary objective:

• To assess the time to progression (TTP) of Docetaxel in combination with Oxaliplatin with or without 5-Fluorouracil (5-FU) or Capecitabine in metastatic or locally recurrent gastric cancer previously untreated with chemotherapy for advanced disease (part II).

Secondary objectives:

• To establish the safety profile.
• To assess the Overall Response Rate (ORR) based on the World Health Organization (WHO) criteria
• To assess the Overall Survival (OS)

Study Overview

• Status: Completed
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Drug: Docetaxel + Oxaliplatin; Drug: Docetaxel + Oxaliplatin + 5-FU; Drug: Docetaxel + Oxaliplatin + Capecitabine

Detailed Description

The purpose of this study (Part II) was to evaluate the time to progression in the 3 arms at an optimal dose level of docetaxel and oxaliplatin defined during a prior pilot (Part I) phase study. The estimated duration of treatment was to be 6 months. Treatment was to be administered up to progression, unacceptable toxicities, or withdrawal of consent. The reason and date of removal of all participants was documented on the case report form.

Participants who ended treatment but had not yet progressed (e.g. unacceptable toxicities or withdrawal of consent) were be followed every 8 weeks with a complete tumor assessment until documented progression or further anti-tumor therapy. Then, they would be followed every 3 months after progression for survival status; date of death or progression were reported. Participants who ended treatment for progression, were to be followed every 3 months until death. Date of death was reported. The planned duration of the study was 30 months.

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Diegem, Belgium
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Germany
  • Frankfurt, Germany
    • Sanofi-Aventis Administrative Office
• Hungary
  • Budapest, Hungary
    • Sanofi-Aventis Administrative Office
• Italy
  • Milan, Italy
    • Sanofi-Aventis Administrative Office
• Portugal
  • Porto Salvo, Portugal
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• Switzerland
  • Genève, Switzerland
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Guildford Surrey, United Kingdom
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Histologically proven gastric adenocarcinoma, including adenocarcinoma of the gastro-oesophageal junction
• Metastatic or locally recurrent disease
• Prior adjuvant (and/or neo-adjuvant) chemotherapy with 5-Fluorouracil, Cisplatin, epirubicin is allowed provided that the patient has relapsed > 12 months after the end of the chemotherapy
• Performance status Karnofsky index > 70
• Hematology within 7 days before randomization:Hemoglobin ≥10g/dl, Absolute Neutrophil Count ≥2.0 10^9/L, platelets ≥100 x 10^9/L
• Blood chemistry within 7 days before randomization:Total bilirubin ≤1x Upper Normal Limit(UNL), Aspartate Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase SGOT) and Alanine Aminotransferase (ALT)Serum Glutamate Pyruvate Transaminase(SGPT) ≤2.5xUNL, alkaline phosphatase ≤ 5x UNL, provided that AST or ALT > 1.5 x UNL is not associated with alkaline phosphatase > 2.5 x UNL; creatinine ≤1.25x UNL or 1.25x UNL < creatinine ≤1.5x UNL and calculated/measured creatinine clearance ≥60 ml/min)
• Measurable and/or evaluable metastatic disease

Exclusion criteria:

• Any prior palliative chemotherapy
• Neurosensory symptoms National Cancer Institute Common Toxicity Criteria for Adverse Events grade≥2

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TE (Taxotere and Eloxatin); Docetaxel (Taxotere) in combination with Oxaliplatin (Eloxatin). Each chemotherapy cycle was repeated every 21 days. Participants received either the optimal or non-optimal dose for Taxotere and Eloxatin. Participants who received the optimal dose for Taxotere and Eloxatin were analyzed in this study.	Drug: Docetaxel + Oxaliplatin; Dose level 1 (non-optimal dose): Docetaxel 75 mg/m² as an 1-hour intravenous (IV) infusion on day 1 followed by Oxaliplatin 100 mg/m² as a two to six-hour IV infusion on day 1 Dose level 2 (optimal dose): Docetaxel 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin 130 mg/m² as a two to six-hour IV infusion on day 1
Experimental: TEF (Taxotere, Eloxatin and 5-FU); Docetaxel (Taxotere) in combination with Oxaliplatin (Eloxatin) and 5-FU (5-Fluorouracil). Each chemotherapy cycle was repeated every 14 days. Participants received either the optimal or non-optimal dose for Taxotere, Eloxatin and 5-FU. Participants who received the optimal dose for Taxotere, Eloxatin and 5-FU were analyzed in this study.	Drug: Docetaxel + Oxaliplatin + 5-FU; Dose level 1 (non-optimal dose): Docetaxel 40 mg/m² as a 1-hour intravenous (IV) infusion day 1; Oxaliplatin 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m2 as a 46-hour continuous infusion day 1. Dose level 2 (optimal dose): Docetaxel 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1.
Experimental: TEX (Taxotere, Eloxatin and Xeloda); Docetaxel (Taxotere) in combination with Oxaliplatin (Eloxatin) and capecitabine (Xeloda). Each chemotherapy cycle was repeated every 21 days. Participants received either the optimal or non-optimal dose for Taxotere, Eloxatin and Xeloda. Participants who received the optimal dose for Taxotere, Eloxatin and Xeloda were analyzed in this study.	Drug: Docetaxel + Oxaliplatin + Capecitabine; Dose level 1 (optimal dose): Docetaxel 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine 625 mg/m2 two times a day continuously. Dose level 2 (non-optimal dose): Docetaxel 65 mg/m² as a 1-hour IV infusion on day 1, Oxaliplatin 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine 625 mg/m² two times a day continuously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression	The number of months measured from the day of randomization to the first tumor progression according to World Health Organization (WHO) criteria evaluation of cancer response, or death from any cause. WHO Criteria for Progressive Disease: ≥ 25% increase in the size of at least one bidimensionally or unidimensionally measurable lesion.	every 8 weeks up to a maximum of 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response Rate (ORR)	Percentage of partial and complete responses, according to WHO criteria: Complete Response: Disappearance of all known disease, determined by 2 observations not less than 4 weeks apart. Partial Response: Decrease by at least 50% of the diameters of all measurable lesions, determined by 2 observations not less than 4 weeks apart.	every 8 weeks up to a maximum of 36 months
Overall Survival (OS)	The number of months measured from the date of randomization to the date of death due to any cause.	up to a maximum of 36 months

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Van Cutsem E, Boni C, Tabernero J, Massuti B, Middleton G, Dane F, Reichardt P, Pimentel FL, Cohn A, Follana P, Clemens M, Zaniboni A, Moiseyenko V, Harrison M, Richards DA, Prenen H, Pernot S, Ecstein-Fraisse E, Hitier S, Rougier P. Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study. Ann Oncol. 2015 Jan;26(1):149-156. doi: 10.1093/annonc/mdu496.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: September 27, 2006
• First Submitted That Met QC Criteria: September 28, 2006
• First Posted (Estimate): September 29, 2006

Study Record Updates

• Last Update Posted (Estimate): January 7, 2013
• Last Update Submitted That Met QC Criteria: December 19, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Capecitabine; Oxaliplatin
• Other Study ID Numbers: DOCOX_C_00082; EudraCT # : 2005-005464-92