Trastuzumab Plus R115777 in Treating Patients With Advanced or Metastatic Cancer

NCT ID: NCT00005842

Last Updated: 2013-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-06-30

Brief Summary

Phase I trial to study the effectiveness of trastuzumab plus R115777 in treating patients who have advanced or metastatic cancer. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with R115777 may kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of R115777 when administered with trastuzumab (Herceptin) in patients with advanced or metastatic adenocarcinoma.

II. Assess the toxicities and pharmacokinetics of this treatment regimen in this patient population.

III. Determine the antitumor activity of this treatment regimen in these patients.

IV. Determine the relative biologic endpoints of this regimen and correlate them with toxicity and pharmacokinetic parameters in these patients.

OUTLINE: This is a dose escalation, multicenter study of R115777.

Patients receive trastuzumab (Herceptin) IV over 90 minutes on days 1, 8, 15, and 22 plus oral R115777 twice daily for 3 weeks. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicities.

Patients are followed every 30 days until toxicity resolves.

Conditions

Cancer

Study Design

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

Study Groups

Arm I

Patients receive trastuzumab (Herceptin) IV over 90 minutes on days 1, 8, 15, and 22 plus oral R115777 twice daily for 3 weeks. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicities.

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

tipifarnib

Intervention Type: DRUG

Interventions

trastuzumab

Intervention Type: BIOLOGICAL

tipifarnib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced or metastatic adenocarcinoma
• Expression of +1 to 3+ HER2/neu on immunohistochemical or immunocytochemistry staining
• No brain metastases unless all of the following is true:

• Previously treated
• Asymptomatic
• Stable dose of decadron
• No evidence of edema

PATIENT CHARACTERISTICS:

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 9.0 g/dL
• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 3 times upper limit of normal (ULN) (no greater than 5 times ULN in case of liver involvement)
• Creatinine no greater than 1.5 mg/dL
• LVEF at least 50% by RVG or MUGA
• No uncontrolled unstable angina
• No history of congestive heart failure or cardiac ischemia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent active infection or serious systemic disorder that would preclude study
• No allergies to imidazole compounds

PRIOR CONCURRENT THERAPY:

• No prior trastuzumab (Herceptin) No other concurrent immunotherapy
• At least 4 weeks since prior chemotherapy (6 weeks since mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy
• No concurrent hormonal cancer therapy except LHRH agonists for prostate cancer
• No concurrent radiotherapy
• No other concurrent experimental medications

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony W. Tolcher, MD

Role: STUDY_CHAIR

San Antonio Cancer Institute

Locations

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Institute for Drug Development

San Antonio, Texas, United States

Countries

United States

References

Schwartz G, Rowinsky EK, Rha SY, et al.: A phase I, pharmacokinetic, and biologic correlative study of R115777 and trastuzumab (herceptin) in patients with advanced cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-322, 2001.

Reference Type: RESULT

Other Identifiers

UTHSC-IDD-99-26

Identifier Type: -

Identifier Source: secondary_id

SACI-IDD-99-26

Identifier Type: -

Identifier Source: secondary_id

NCI-62

Identifier Type: -

Identifier Source: secondary_id

CDR0000067858

Identifier Type: -

Identifier Source: org_study_id