Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Trastuzumab and Flavopiridol in Treating Patients With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	DFCI-01177 NCI-5867, NCT00039455, 5867

Special Category: SPORE trial

Objectives

1. Determine the safety, tolerability, and maximum tolerated dose of flavopiridol when combined with trastuzumab (Herceptin) in patients with HER2-positive metastatic breast cancer.
2. Determine the dose of flavopiridol necessary to achieve a target plasma level of 300-500 nanomoles/L when combined with a fixed dose of trastuzumab in these patients.
3. Assess the feasibility of measuring cyclin D1 in circulating tumor cells and tissue biopsies before and after this regimen as a surrogate marker of flavopiridol activity in these patients.
4. Monitor target activity of this regimen in plasma, circulating tumor cells, and tissue biopsies from these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed stage IV breast cancer
  • Patients without histologic or cytologic confirmation of metastatic disease must have unequivocal evidence of metastasis by physical examination or radiologic study



• Primary tumor or metastasis HER2-positive by one of the following:
  • Immunohistochemistry (3+ positive using the DAKO Herceptest or the CB-11 antibody)
  • Fluorescence in situ hybridization (positive by either the Vysis Pathvysion™ method or the Ventana INFORM™ method)



• Measurable or evaluable disease



• No active brain metastases or leptomeningeal carcinomatosis
  • Previously treated CNS metastases allowed provided there are no active symptoms from the CNS disease



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• No more than 2 prior trastuzumab-containing regimens for metastatic disease

Chemotherapy:

• No more than 3 prior chemotherapy regimens for metastatic disease
• No other concurrent chemotherapy

Endocrine therapy:

• Prior hormonal therapy in the adjuvant or metastatic setting allowed
• Leuprolide initiated prior to study allowed provided therapy continues throughout study
• No other concurrent hormonal therapy

Radiotherapy:

• At least 1 week since prior radiotherapy for metastatic or early-stage breast cancer
• No concurrent radiotherapy
  • Whole brain radiotherapy or stereotactic radiosurgery for brain metastases allowed provided study therapy is held during and for 1 week after radiotherapy

Surgery:

• Not specified

Other:

• Recovered from prior anticancer treatments
• No other concurrent experimental treatments
• Concurrent bisphosphonates initiated before study allowed
• Concurrent bisphosphonates initiated during study allowed provided there has been no evidence of progressive disease and the bone sites do not constitute the only sites of evaluable disease

Patient Characteristics:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1

  OR

• Karnofsky 70-100%

Life expectancy:

• More than 6 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 3 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• LVEF at least 50% by echocardiogram or nuclear scintigraphy (e.g., MUGA scan or radionuclide ventriculography)
• No acute changes on electrocardiogram
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• Prior grade 1 or 2 allergic reactions to trastuzumab (Herceptin) allowed if these reactions did not prevent further administration
• No prior grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biological composition to study agents
• No contraindication to warfarin or other warfarin products
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

A total of 30-50 patients will be accrued for this study.

Outline

This is a multicenter, dose-escalation study of flavopiridol.

Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose is determined (MTD). The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 10 patients receives flavopiridol at the MTD and trastuzumab on the once weekly schedule to assess the true toxicity rate. A second cohort of 10 patients receives flavopiridol at the MTD and trastuzumab once every 21 days to assess the tolerability of this schedule.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Lyndsay Harris, MD, Protocol chair(Contact information may not be current)		Ph: 617-632-6363; 866-790-4500 Email: lharris@partners.org

Registry Information
Official Title		A Phase I Study Of Herceptin/Flavopiridol In HER-2 Positive Metatatic Breast Cancer
Trial Start Date		2002-01-31
Registered in ClinicalTrials.gov		NCT00039455
Date Submitted to PDQ		2002-04-23
Information Last Verified		2005-03-24
NCI Grant/Contract Number		CA06516

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