Docetaxel and Oxaliplatin in Gastric Cancer

Stomach Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00382720
• Other study ID #: DOCOX_C_00082
• Secondary ID: EudraCT # : 2005
• Status: Completed
• Phase: Phase 2
• First received: September 27, 2006
• Last updated: December 19, 2012
• Start date: September 2006
• Est. completion date: April 2010

Study information

• Verified date: December 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stomach Neoplasms

Intervention

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
• 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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Hungary,  Italy,  Portugal,  Russian Federation,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No