Gemcitabine Hydrochloride and Genistein in Treating Women With Stage IV Breast Cancer

Phase II Trial of Gemcitabine and Genistein in Metastatic Breast Cancer Patients With Biomarker Assays

RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and genistein, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine hydrochloride together with genistein may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine hydrochloride together with genistein works in treating women with stage IV breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Dietary supplement: genistein; Drug: gemcitabine; Procedure: Tumor biopsy

Detailed Description

OBJECTIVES:

Primary

• Determine the objective response rate in patients with stage IV breast cancer treated with gemcitabine hydrochloride and genistein.

Secondary

• Determine the duration of response and survival of patients treated with this regimen.
• Determine the time to disease progression in patients treated with this regimen.
• Determine the quantitative and qualitative toxic effects of this regimen in these patients.
• Correlate plasma genistein levels with response in patients treated with this regimen.

OUTLINE: Patients receive oral genistein once daily on days -7 to 1. Patients also receive gemcitabine hydrochloride IV on days 1 and 8 and oral genistein once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

  • Stage IV disease
  • Clinical and/or radiological evidence of metastatic disease

• Measurable disease

  • Prior radiotherapy allowed provided there is ≥ 1 measurable disease site outside the radiation field

• No active CNS metastases

  • Previously treated CNS metastases allowed provided disease is stable for ≥ 3 months without steroids or antiseizure medications

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Not specified

Performance status

• SWOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin ≤3.0 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No serious systemic disorder that would preclude study compliance
• No history of another malignancy except curatively treated carcinoma of the cervix or basal cell or squamous cell skin cancer in complete remission
• No unresolved bacterial infection requiring antibiotic treatment
• No known HIV-1 positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 weeks since prior biologic therapy

Chemotherapy

• Prior adjuvant chemotherapy allowed

• Prior adjuvant or neoadjuvant taxane-based therapy or taxane therapy for metastatic disease allowed

  • Patient must have failed therapy within 2 years after completion of treatment
• At least 3 weeks since prior chemotherapy
• No more than 2 prior cytotoxic chemotherapy regimens for metastatic disease
• No prior gemcitabine hydrochloride
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

• At least 2 weeks since prior and no concurrent hormonal therapy

  • Must have documented disease progression during prior hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior surgery

Other

• At least 3 weeks since prior investigational therapy

• At least 1 week since prior soy supplements (e.g., soy-based pills, liquids, or concentrates)

  • Dietary soy as part of a meal (e.g., tofu) allowed once a week

• No concurrent nutritional supplements, herbal agents, or high doses of antioxidants (e.g., vitamins C, D, or E) that may interact with, antagonize, alter, or imitate the potential effects of gemcitabine hydrochloride or genistein

  • A single daily multivitamin is allowed
• No other concurrent immunotherapy
• No other concurrent experimental medication
• Concurrent anticoagulants, appetite stimulants, and replacement steroids allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine, genistein (Novasoy), Tumor biopsy; Gemcitabine IV-1000mg/m2: Days 1 & 8 every 21 days Novasoy Orally-100 mg 2 times/day for 7 days; 2 times/day on Days 1-21 every 21 days.	Dietary supplement: genistein; Novasoy Orally-100 mg 2 times/day for 7 days; 2 times/day on Days 1-21 every 21 days.; Other Names: Novasoy; Drug: gemcitabine; Gemcitabine IV-1000mg/m2: Days 1 & 8 every 21 days; Other Names: Gemcitabine hydrochloride; Gemzar®; Procedure: Tumor biopsy; Biopsy of tumor prior to dose of genistein (Novasoy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate by RECIST Criteria Following	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	every 2 courses until disease progression or death, up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response	From the time the last patient comes off study treatment for one year
Overall Survival	From the time the last patient comes off study treatment for one year to monitor survival
Time to Disease Progression	From the time that treatment is initiated until the time restaging indicates progressive disease.
Duration of Survival	At 1 year following study treatment
Qualitative and Quantitative Toxicities	30 days following treatment
Correlate Responses With Plasma Genistein Levels	At course 1 day -7, course 1 day -1 (before and 4 hours after dose), course 2 day 1 (before and 4 hours after dose)
In Vivo Effects of Genistein in Breast Cancer Tissue Biomarkers (Ki67, TUNEL Assay, p-Akt, NF-kB, Immunohistochemistry and cDNA Microarray Analysis)	At baseline (pre-genistein treatment) and 7 days following genistein treatment

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amy Weise, DO, Barbara Ann Karmanos Cancer Institute

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimated): October 27, 2005

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Anticarcinogenic Agents; Phytoestrogens; Genistein; Gemcitabine
• Other Study ID Numbers: 2597; P30CA022453 (U.S. NIH Grant/Contract); WSU-C-2597 (Other Identifier: Barbara Ann Karmanos Cancer Institute)