Docetaxel, Oxaliplatin, and Fluorouracil in Treating Patients With Metastatic or Unresectable Stomach Cancer, Gastroesophageal Junction Cancer, or Other Solid Tumor

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00711243
First received: July 5, 2008
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given with oxaliplatin and fluorouracil and to see how well they work in treating patients with metastatic or unresectable stomach cancer, gastroesophageal junction cancer, or other solid tumor.


Condition Intervention Phase
Gastric Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: docetaxel
Drug: fluorouracil
Drug: oxaliplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Maximum tolerated dose of docetaxel when given in combination with oxaliplatin and fluorouracil (Phase I) [ Time Frame: After completion of 1 cycle of therapy (1 cycle = 14 days) ] [ Designated as safety issue: Yes ]
  • Response rate in patients with adenocarcinoma of the stomach or gastroesophageal junction (Phase II) [ Time Frame: After 4 cycles of therapy (1 cycle = 14 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dose-limiting toxicity of docetaxel when given in combination with oxaliplatin and fluorouracil [ Time Frame: After 1 cycle of therapy (1 cycle = 14 days) ] [ Designated as safety issue: Yes ]
  • Frequency of CYP3A4, CYP3A5, and MDR polymorphisms and their impact on docetaxel toxicity [ Time Frame: Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle ] [ Designated as safety issue: Yes ]
  • Frequency of XRCC1 and ERCC2 polymorphisms and their impact on oxaliplatin toxicity [ Time Frame: Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle ] [ Designated as safety issue: Yes ]
  • Frequency of DPD and TSER polymorphisms and their impact on fluorouracil toxicity [ Time Frame: Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle ] [ Designated as safety issue: Yes ]
  • Toxicity profile [ Time Frame: Day 1 of each cycle of therapy ] [ Designated as safety issue: Yes ]

Enrollment: 58
Study Start Date: March 2005
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1a
Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
Drug: docetaxel
Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.
Drug: fluorouracil
Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.
Drug: oxaliplatin
Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 2a
Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
Drug: docetaxel
Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.
Drug: fluorouracil
Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.
Drug: oxaliplatin
Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 3a
Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
Drug: docetaxel
Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.
Drug: fluorouracil
Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.
Drug: oxaliplatin
Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 4a
Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
Drug: docetaxel
Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.
Drug: fluorouracil
Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.
Drug: oxaliplatin
Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 5a
Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
Drug: docetaxel
Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.
Drug: fluorouracil
Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.
Drug: oxaliplatin
Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Detailed Description:

OBJECTIVES:

Primary

  • To establish the maximum tolerated dose of docetaxel when administered with oxaliplatin and fluorouracil in patients with metastatic or unresectable solid tumors. (Phase I)
  • To determine the response rate in patients with metastatic or unresectable adenocarcinoma of the stomach or gastroesophageal junction treated with this regimen. (Phase II)

Secondary

  • To determine the dose limiting toxicity of this regimen in these patients.
  • To evaluate the frequency of CYP3A4, CYP3A5, and MDR polymorphisms and their impact on toxicity of docetaxel.
  • To evaluate the frequency of XRCC1 and ERCC2 polymorphisms and their impact on the toxicity of oxaliplatin.
  • To evaluate the frequency of DPD and TSER polymorphisms and their impact on the toxicity of fluorouracil.
  • To characterize the toxicity profile of this regimen in these patients.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for at least 2 courses in the absence of disease progression, symptomatic tumor progression, or unacceptable toxicity.

Patients undergo blood sample collection periodically for pharmacokinetic and pharmacogenomic correlative studies. Plasma concentrations of docetaxel are analyzed by reverse-phase high performance liquid chromatography and tandem mass spectrometry. Polymorphisms in CYP3A4/5, MDR, and other genes are analyzed by PCR.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 73 patients (30 for phase I and 43 for phase II) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic or surgically unresectable solid tumor meeting 1 of the following criteria:

    • Any solid tumor (Phase I)
    • Adenocarcinoma of the stomach or gastroesophageal junction (Phase II)
  • Unidimensionally measurable disease by CT scan or MRI
  • No uncontrolled brain metastasis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin normal
  • Meets 1 of the following criteria:

    • Alkaline phosphatase (AP) normal AND AST or ALT ≤ 5 times ULN
    • AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
    • AP ≤ 5 times ULN AND AST or ALT normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy
  • No preexisting neuropathy
  • No concurrent uncontrolled illness or other condition that would preclude study compliance
  • No history of severe hypersensitivity reaction to docetaxel or to other drugs formulated with polysorbate 80
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study

PRIOR CONCURRENT THERAPY:

  • Recovered from prior therapy
  • More than 4 weeks since prior therapy (Phase I)
  • No prior oxaliplatin or taxanes (Phase I)
  • More than 4 weeks since prior radiotherapy (Phase I)
  • No more than two prior therapies for metastatic disease (Phase I)
  • No prior therapy for metastatic disease (Phase II)
  • At least 6 months since prior adjuvant therapy (given prior to the occurrence of metastatic disease) (Phase II)
  • Prior fluorouracil and concurrent radiotherapy for palliation of the primary tumor allowed provided metastatic disease is present outside the radiotherapy field (Phase II)
  • No prior radiotherapy to ≥ 30% of bone marrow
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711243

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Mary Mulcahy, MD Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00711243     History of Changes
Other Study ID Numbers: NU 04I2, P30CA060553, NU-0412, SANOFI - AVENTIS-NU0412, NU-948-006, STU00006778
Study First Received: July 5, 2008
Last Updated: July 7, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Northwestern University:
unspecified adult solid tumor, protocol specific
adenocarcinoma of the stomach
stage III gastric cancer
stage IV gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Docetaxel
Oxaliplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014