Trastuzumab Plus R115777 in Treating Patients With Advanced or Metastatic Cancer

Cancer Clinical Trial

Official title:

A Phase I, Pharmacokinetic, and Biologic Correlative Study of R115777 (NSC 702818) and Herceptin in Patients With Advanced Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005842
• Other study ID #: CDR0000067858
• Secondary ID: UTHSC-IDD-99-26S
• Status: Completed
• Phase: Phase 1
• First received: June 2, 2000
• Last updated: February 8, 2013
• Start date: June 2000

Study information

• Verified date: April 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: February 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Biological:
• trastuzumab

Drug:
• tipifarnib

Locations

Country	Name	City	State
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Institute for Drug Development	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, 200