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A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors


I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan
hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP
glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7).

II. To identify any activity of this treatment combination in patients with metastatic

III. To examine the differences in the toxicity profile, especially pertaining to
hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination
of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes.

IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its

OUTLINE: This is a dose-escalation study. Patients are stratified according to UGT1A1
genotype (6/6 vs 6/7 [closed to accrual as of 8/24/06] vs 7/7).

Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin
IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (QD) on days 2-15. Courses
repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride, oxaliplatin,
and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as
the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting
toxicity. Once the MTD is determined, an additional 6-10 patients (for a total of 12
patients) receive treatment at that dose.

After completion of study treatment, patients are followed up at 3 months.

PROJECTED ACCRUAL: A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II
[closed to accrual as of 8/24/06], and 24-34 for stratum III) will be accrued for this study
within approximately 4.4 years.

Inclusion Criteria:

- Histologically confirmed solid tumor for which there is no known standard therapy
that is potentially curative or capable of extending life expectancy

- Unresectable disease

- Willing to provide biologic specimens to determine UGT1A1 genotype

- No CNS metastases

- Prior CNS metastases allowed provided patient was treated with surgery and/or
radiotherapy and is stable for more than 8 weeks

- Performance status - ECOG 0-2

- At least 12 weeks

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 9.0 g/dL

- Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1
genotype (1.5 times ULN for patients with 6/7 [closed to accrual as of 8/24/06] or
7/7 UGT1A1 genotype)

- AST no greater than 3 times ULN (5 times ULN if there is liver involvement)

- Creatinine no greater than 1.5 times ULN

- No New York Heart Association class III or IV heart disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergy to platinum compounds, irinotecan, or to antiemetics or
antidiarrheals appropriate for administration with study therapy

- No uncontrolled infection

- No seizure disorder

- No peripheral neuropathy grade 2 or greater

- More than 4 weeks since prior biologic therapy

- More than 4 weeks since prior immunotherapy

- No concurrent immunotherapy

- No concurrent prophylactic colony-stimulating factor therapy

- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
and recovered

- No other concurrent chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy to more than 25% of the bone marrow

- No concurrent radiotherapy

- See Disease Characteristics

- No other concurrent investigational therapy

- No concurrent sorivudine, brivudine, lamivudine, or stavudine

- No concurrent enrollment in any other study involving a pharmacologic agent for
symptom control or therapeutic intent

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0

Outcome Time Frame:

3 weeks

Safety Issue:


Principal Investigator

Matthew Goetz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

November 2003

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Mayo Clinic Rochester, Minnesota  55905