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Trastuzumab Plus R115777 in Treating Patients With Advanced or Metastatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005842
First received: June 2, 2000
Last updated: February 8, 2013
Last verified: April 2007
History of Changes
  Purpose

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.


Condition Intervention Phase
Cancer
 Biological: trastuzumab
Drug: tipifarnib
 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Pharmacokinetic, and Biologic Correlative Study of R115777 (NSC 702818) and Herceptin in Patients With Advanced Cancer

Resource links provided by NLM:

Drug Information available for: Trastuzumab
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Enrollment: 24
Study Start Date: June 2000
Primary Completion Date: February 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.
 Biological: trastuzumab Drug: tipifarnib

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005842

Locations
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Institute for Drug Development
San Antonio, Texas, United States, 78245-3217
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Study Chair: Anthony W. Tolcher, MD San Antonio Cancer Institute
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

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.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005842     History of Changes
Other Study ID Numbers: CDR0000067858, UTHSC-IDD-99-26, SACI-IDD-99-26, NCI-62
Study First Received: June 2, 2000
Last Updated: February 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage III colon cancer
stage IV colon cancer
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage III gastric cancer
stage IV gastric cancer
recurrent gastric cancer
occult non-small cell lung cancer
stage IIIB breast cancer
recurrent non-small cell lung cancer
stage III pancreatic cancer
recurrent pancreatic cancer
stage III rectal cancer
stage IV rectal cancer
 recurrent colon cancer
recurrent rectal cancer
stage IV anal cancer
recurrent anal cancer
stage III esophageal cancer
stage IV esophageal cancer
stage IIIA anal cancer
stage IIIB anal cancer
recurrent esophageal cancer
stage III cervical cancer
recurrent cervical cancer
stage IVB cervical cancer
stage IVA cervical cancer
inflammatory breast cancer
stage III renal cell cancer

Additional relevant MeSH terms:
Trastuzumab
Tipifarnib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013