Official Title: “A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil”

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.

Study Type: Interventional

Study Design: Treatment

Study Primary Completion Date: May 2009

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.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: fluorouracil
• Drug: oxaliplatin
• Genetic: polymerase chain reaction
• Genetic: polymorphism analysis
• Other: high performance liquid chromatography
• Other: mass spectrometry
• Other: pharmacogenomic studies
• Other: pharmacological study

Primary Measures

• Maximum tolerated dose of docetaxel when given in combination with oxaliplatin and fluorouracil in patients with solid tumors (Phase I)
  • Safety Issue?: Yes
• Response rate in patients with adenocarcinoma of the stomach or gastroesophageal junction (Phase II)
  • Safety Issue?: No

Secondary Measures

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

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Robert H. Lurie Cancer Center

Overall Clinical Trial Officials and Contacts

Mary Mulcahy, MD Principal Investigator Robert H. Lurie Cancer Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00711243

Study ID Number: CDR0000599734

ClinicalTrials.gov Identifier: NCT00711243

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database