Trastuzumab Plus R115777 In Treating Patients With Advanced Or Metastatic Cancer

Study Overview

Trastuzumab Plus R115777 in Treating Patients With Advanced or Metastatic Cancer

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.

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.

Cancer

BIOLOGICAL: trastuzumab
DRUG: tipifarnib

CDR0000067858
UTHSC-IDD-99-26
SACI-IDD-99-26
NCI-62

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2000-06-02	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-02-08
First Submitted that Met QC Criteria 2004-04-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-02-11
First Posted (ESTIMATED) 2004-04-26	Results First Posted N/A	Last Verified 2007-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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 recei	BIOLOGICAL: trastuzumab DRUG: tipifarnib

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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 recei

BIOLOGICAL: trastuzumab

DRUG: tipifarnib

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Anthony W. Tolcher, MD, San Antonio Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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Clinical Trial Record