Know Cancer

forgot password

Phase I Trial of R115777 and OSI-774 in Patients With Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Phase I Trial of R115777 and OSI-774 in Patients With Advanced Solid Tumors


I. Determine the maximum tolerated dose of erlotinib in combination with tipifarnib in
patients with advanced solid tumors.

II. Determine the toxicity profile of this regimen in these patients. III. Determine the
effect of erlotinib on the disposition of tipifarnib in these patients.

IV. Determine in vitro markers of farnesyl transferase inhibition and epidermal growth
factor receptor inhibition in patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive oral erlotinib once daily on days 1-28 and oral tipifarnib twice daily on
days 1-21. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib and tipifarnib 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 (closed to accrual as of

Once the MTD is determined, up to 12 additional patients are treated at that dose. Patients
receive oral tipifarnib as above and oral erlotinib once daily on days 1-28 (days 8-28 of
course 1 only). Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 18-42 patients (12 treated at the maximum tolerated dose) will
be accrued for this study.

Inclusion Criteria:

- Histologically confirmed advanced solid tumor

- Unresectable disease

- Not amenable to potentially curative or standard life-prolonging therapy

- Tumor amenable to serial biopsy (for patients treated at the maximum tolerated dose

- Brain metastases allowed provided the following criteria are met:

- Treated with prior surgery and/or radiotherapy

- Disease has been stable for ≥ 8 weeks

- No concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin,
or carbamazepine)

- Performance status - ECOG 0-1

- At least 12 weeks

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 2 mg/dL

- Creatinine ≤ 1.5 times ULN

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

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or

- No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production

- No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)

- No congenital abnormality (e.g., Fuch's dystrophy)

- No requirement for IV alimentation

- No gastrointestinal tract disease resulting in the inability to take oral or
nasogastric medication

- No active peptic ulcer disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraceptive

- No significant traumatic injury within the past 21 days

- No active or uncontrolled infection

- No other concurrent uncontrolled illness

- No psychiatric illness or social situation that would preclude study compliance

- More than 4 weeks since prior immunotherapy or biologic therapy

- No prior cetuximab

- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) for prophylaxis

- No concurrent immunotherapy

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

- No concurrent chemotherapy

- More than 4 weeks since prior hormonal therapy for cancer

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy

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

- No concurrent radiotherapy

- See Disease Characteristics

- More than 21 days since prior major surgery

- No prior surgical procedure affecting gastrointestinal absorption

- No prior farnesyl transferase inhibitors (e.g., tipifarnib, SCH-66336, or

- No other prior epidermal growth factor receptor-targeting therapies (e.g., ZD-1869,
EKB-569, erlotinib, CI-1033, GW572016, or EMD 72000)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational therapy

Type of Study:


Study Design:

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

Outcome Measure:

Number and severity of all adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

Outcome Description:

Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

Outcome Time Frame:

Up to 30 days after last study treatment

Safety Issue:


Principal Investigator

Julian Molina

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2004

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Mayo Clinic Rochester, Minnesota  55905