Cisplatin and Radiation Therapy in Treating Patients with Stage II-III Triple Negative Breast Cancer

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Status: Active

Description

This phase I trial studies the side effects and the best dose of cisplatin when given together with radiation therapy in treating patients with stage II-III breast cancer that does not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 (HER2) / neu protein. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving cisplatin together with radiation therapy may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • The primary tumor must be triple negative breast cancer (i.e., the invasive tumor must be estrogen receptor [ER]-negative and progesterone receptor [PR]-negative, or stain < 10% by immunohistochemistry [IHC]; the invasive tumor must be HER2-negative, defined as 0 or 1+ by IHC or fluorescent in situ hybridization [FISH] < 2.0)
  • Breast-conserving surgery or mastectomy with surgical excision of all gross disease with negative surgical margins
  • Participants undergoing definitive surgery at diagnosis must have pathologic stage II or III disease
  • Participants undergoing preoperative systemic therapy must have clinical stage II or III disease at presentation (clinical stage I disease is excluded)
  • Participants undergoing preoperative systemic therapy must have residual invasive disease in the breast or axillary lymph nodes at the time of definitive surgery
  • Any prior systemic therapy is permitted (except cisplatin or carboplatin)
  • Minimum 3-week interval from last chemotherapy administration and last breast surgery to radiation
  • Maximum 8-week interval from last chemotherapy administration or last breast surgery (whichever is more recent) to radiation
  • Absolute neutrophil count greater than 1500/mm^3
  • Platelet count greater than 100,000/mm^3
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 times upper limit of normal
  • Bilirubin =< 1.5 mg/dl
  • Glomerular filtration rate (GFR) >= 60 ml/min
  • Negative urine pregnancy test within 2 weeks of registration for women of child-bearing potential; women of child-bearing potential must have a documented negative pregnancy test and agree to use adequate contraception throughout the study period
  • Ability and willingness to sign written informed consent
  • Patients with tumors of two different subtypes will be eligible provided that the triple negative tumor otherwise meets eligibility requirements, and the non-triple negative tumor is < 1.0 cm in size
  • Patients with inflammatory breast cancer are eligible for the escalation phase of the mastectomy cohort

Exclusion Criteria

  • Prior radiation therapy to the breast or ipsilateral regional nodes not allowed (a history of radiation therapy to other sites is permissible)
  • Ongoing therapy with other investigational agents
  • Hormonal therapy (tamoxifen, an aromatase inhibitor, or Lupron) is not permitted during radiation or during the subsequent 4 weeks (the entire dose-limiting toxicity [DLT] window)
  • Unresolved toxicity from other agents; participants with unresolved or unstable Common Toxicity Criteria Adverse Event version 4 (CTCAE v4) grade 2 or greater toxicity from prior administration of another anti-cancer treatment are not eligible
  • Significant comorbidity: ineligible participants include those with clinically significant and uncontrolled major cardiac, respiratory, renal hepatic, gastrointestinal, hematologic, or neurologic/psychiatric disease or disorder, including, but not limited to: active or uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, or any other illness or condition that could exacerbate potential toxicities, confound safety assessment or limit compliance with study requirements
  • Pregnant women are excluded from this study
  • Pathologic complete response following preoperative chemotherapy
  • Participants with biopsy proven metastatic disease (M1)
  • Peripheral neuropathy greater than grade 1
  • Hearing loss greater than grade 1
  • Inflammatory breast cancer patients are ineligible, except in the escalation phase of the mastectomy cohort

Locations & Contacts

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Contact: Jennifer Ruth Bellon
Phone: 617-632-3591 Email: jbellon@lroc.harvard.edu
Dana-Farber Cancer Institute
Status: Active
Contact: Jennifer Ruth Bellon
Phone: 617-632-3591 Email: jbellon@lroc.harvard.edu
Charlestown
Massachusetts General Hospital
Status: Active
Contact: Steven Jay Isakoff
Phone: 781-624-4700 Email: sisakoff@partners.org
Milford
Dana-Farber / Brigham and Women's Cancer Center at Milford Regional
Status: Active
Contact: Tatiana I. Lingos
Phone: 508-488-3835 Email: tlingos@partners.org
South Weymouth
Dana-Farber / Brigham and Women's Cancer Center at South Shore
Status: Active
Contact: Tatiana I. Lingos
Phone: 508-488-3835 Email: tlingos@partners.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the safety, tolerability, and maximum tolerated dose (MTD) of cisplatin when given concurrently with radiation therapy for participants with stage II or III breast cancer who have undergone breast conserving surgery.

SECONDARY OBJECTIVES:

I. To assess local recurrence at 5-years in participants receiving cisplatin concurrently with radiation (radiation therapy), as compared with historic controls receiving radiation without concurrent chemotherapy.

II. To assess long-term toxicity in participants receiving cisplatin concurrently with radiation.

OUTLINE: This is a dose-escalation study of cisplatin.

Patients receive cisplatin intravenously (IV) once weekly and undergo radiation therapy daily 5 days a week. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 months and then every 6 months for 5 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Jennifer Ruth Bellon

Trial IDs

Primary ID 12-283
Secondary IDs NCI-2012-02219
Clinicaltrials.gov ID NCT01674842