Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer

NCT00616122 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 057519NCI-2011-01275
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of sunitinib when given together with cyclophosphamide and methotrexate to see how well they work in treating patients with metastatic breast cancer.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IV breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Sunitinib (Phase I)

  Patients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature \> 38.5 degrees Celsius or 3 readings of oral temperature \> 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment. 5\) Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.

  8 weeks

• Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II)

  Progression defined as: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), or appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).

  up to 12 weeks after treatment start date

Secondary Outcomes (2)

• Overall Response Rate

  until disease progression, up to 13 months post treatment

• Duration of Response

  until disease progression up to 13 months post treatment

Study Arms (1)

Sunitinib, Cyclophosphamide, and Methotrexate

EXPERIMENTAL

Drug: cyclophosphamide; Drug: methotrexate; Drug: sunitinib malate; Other: laboratory biomarker analysis

Interventions

cyclophosphamide DRUG

Sunitinib, Cyclophosphamide, and Methotrexate

methotrexate DRUG

Sunitinib, Cyclophosphamide, and Methotrexate

sunitinib malate DRUG

Sunitinib, Cyclophosphamide, and Methotrexate

laboratory biomarker analysis OTHER

Sunitinib, Cyclophosphamide, and Methotrexate

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Pathologically confirmed diagnosis of breast cancer with documented progressive disease * Metastatic disease * Measurable disease as defined by RECIST criteria or evaluable disease * Must have received at least one prior chemotherapy regimen for metastatic breast cancer * Patients refusing all other chemotherapy for breast cancer may enroll without prior treatment * Patients with HER2-overexpression disease must have been previously treated with trastuzumab (Herceptin®) * Patients with stable brain metastases are eligible * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Menopausal status not specified * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Life expectancy ≥ 12 weeks * Absolute Neutrophil Count (ANC) ≥ 1,000/mm³ * Platelet count ≥ 100,000/mm³ * Creatinine ≤ 1.5 times upper limit of normal (ULN) * aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases) * Total bilirubin ≤ 1.5 times ULN * Able to take oral medications and maintain hydration * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after treatment * No severe concurrent illness including, but not limited to, any of the following: * Congestive heart failure * Significant cardiac disease * Uncontrolled hypertension * Must be able to read and speak English PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 2 weeks since prior treatment, including chemotherapy, hormonal therapy, trastuzumab (Herceptin®), or other targeted therapies * Prior bevacizumab allowed if discontinued for any reason other than toxicity * No potent inducers or inhibitors of CYP3A4 enzymes that effect the metabolism of sunitinib malate * No prior sunitinib malate * No other concurrent investigational therapy * No concurrent radiotherapy * Concurrent bisphosphonates allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Cyclophosphamide; Methotrexate; Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Indoles

Limitations and Caveats

Based on published literature indicating significant toxicity and low response rate for combination sunitinib in the treatment of advanced breast cancer, the PI and Breast Oncology Site Committee closed enrollment after accrual of 32 participants.

Results Point of Contact

• Title: Hope S. Rugo
• Organization: University of California, San Francisco

clinicaltrials@ucsf.edu

877-827-3222

Study Officials

• Hope S. Rugo, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2008
• First Posted: February 15, 2008
• Study Start: March 1, 2006
• Primary Completion: March 1, 2011
• Study Completion: December 1, 2012
• Last Updated: January 13, 2020
• Results First Posted: February 12, 2013

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)