Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	NU-0412 SANOFI - AVENTIS-NU0412, NU 04I2, NU-948-006, NCT00711243

Objectives

Primary

1. To establish the maximum tolerated dose of docetaxel when administered with oxaliplatin and fluorouracil in patients with metastatic or unresectable solid tumors. (Phase I)
2. 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

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

Entry 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

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

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

Expected Enrollment

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

Outcomes

Maximum tolerated dose of docetaxel when given in combination with oxaliplatin and fluorouracil in patients with solid tumors (Phase I)
Response rate in patients with adenocarcinoma of the stomach or gastroesophageal junction (Phase II)

Dose-limiting toxicity of docetaxel when given in combination with oxaliplatin and fluorouracil
Frequency of CYP3A4, CYP3A5, and MDR polymorphisms and their impact on docetaxel toxicity
Frequency of XRCC1 and ERCC2 polymorphisms and their impact on oxaliplatin toxicity
Frequency of DPD and TSER polymorphisms and their impact on fluorouracil toxicity
Toxicity profile

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.

Trial Contact Information

Trial Lead Organizations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Mary Mulcahy, MD, Principal investigator		Ph: 312-695-6180

Registry Information
Official Title		A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil
Trial Start Date		2005-03-03
Trial Completion Date		2009-05-31 (estimated)
Registered in ClinicalTrials.gov		NCT00711243
Date Submitted to PDQ		2008-06-26
Information Last Verified		2009-07-05
NCI Grant/Contract Number		CA60553

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