A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil
18 Years
N/A
Both
Gastric Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of docetaxel when given in combination with oxaliplatin and fluorouracil (Phase I)
Outcome Time Frame:
After completion of 1 cycle of therapy (1 cycle = 14 days)
Safety Issue:
Yes
Principal Investigator
Mary Mulcahy, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Robert H. Lurie Cancer Center
Authority:
United States: Federal Government
Study ID:
NU 04I2
NCT ID:
NCT00711243
Start Date:
March 2005
Completion Date:
December 2015
Related Keywords:
- Gastric Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- adenocarcinoma of the stomach
- stage III gastric cancer
- stage IV gastric cancer
- Stomach Neoplasms
Name | Location |
|---|---|
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
