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

NCT ID: NCT00711243

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-20
• Study Completion Date: 2011-02-25

Brief Summary

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.

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.

Conditions

Gastric Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1a

Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

fluorouracil

Intervention Type: DRUG

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Cohort 2a

Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

fluorouracil

Intervention Type: DRUG

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Cohort 3a

Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

fluorouracil

Intervention Type: DRUG

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Cohort 4a

Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

fluorouracil

Intervention Type: DRUG

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Cohort 5a

Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

fluorouracil

Intervention Type: DRUG

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Interventions

docetaxel

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

Intervention Type: DRUG

fluorouracil

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

Intervention Type: DRUG

oxaliplatin

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Mulcahy, MD

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Countries

United States

References

Rosenberg AJ, Rademaker A, Hochster HS, Ryan T, Hensing T, Shankaran V, Baddi L, Mahalingam D, Mulcahy MF, Benson AB 3rd. Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long-Term Follow-Up. Oncologist. 2019 Aug;24(8):1039-e642. doi: 10.1634/theoncologist.2019-0330. Epub 2019 May 28.

Reference Type: DERIVED

PMID: 31138725 (View on PubMed)

Other Identifiers

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

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NU-0412

Identifier Type: -

Identifier Source: secondary_id

SANOFI - AVENTIS-NU0412

Identifier Type: -

Identifier Source: secondary_id

NU-948-006

Identifier Type: -

Identifier Source: secondary_id

STU00006778

Identifier Type: OTHER

Identifier Source: secondary_id

NU 04I2

Identifier Type: -

Identifier Source: org_study_id