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

Sponsor:	Northwestern University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00711243

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 I Phase II

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:

MedlinePlus related topics: Cancer Stomach Cancer

Drug Information available for: Fluorouracil Oxaliplatin Docetaxel

U.S. FDA Resources

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 2013
Estimated Primary Completion Date:	December 2011 (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

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Mary Mulcahy, MD

Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Mary Mulcahy, Robert H. Lurie Comprehensive Cancer Center at Northwestern University
ClinicalTrials.gov Identifier:	NCT00711243 History of Changes
Other Study ID Numbers:	NU 04I2, P30CA060553, NU-0412, SANOFI - AVENTIS-NU0412, NU-948-006
Study First Received:	July 5, 2008
Last Updated:	May 19, 2011
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
Fluorouracil
Oxaliplatin

Docetaxel
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012