Panitumumab, Gemcitabine and Carboplatin in Triple-Negative Metastatic Breast Cancer

NCT ID: NCT00894504

Last Updated: 2015-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2014-09-30

Brief Summary

In this Phase II trial, the investigators will evaluate the combination of gemcitabine, carboplatin, and panitumumab in the treatment of patients with metastatic triple-negative breast cancer. In addition, to assess the efficacy of this combination, tumor tissue will be examined for the presence of various markers, including K-ras and PI3K-activating mutations, EGFR, PTEN, and p53. Correlation of tumor response with marker expression may define a patient subset that is particularly responsive to treatment with a panitumumab-containing combination.

Detailed Description

All patients will receive a pre-emptive skin care regimen during panitumumab therapy to reduce skin toxicity. Treatment cycles will be repeated every 14 days (2 weeks). During each treatment, panitumumab will be administered first, then carboplatin, then gemcitabine. All drugs will be administered according to standard guidelines. Patients will be re-evaluated for response after completion of 3 cycles (6 weeks) of treatment. Patients with objective response or stable disease will continue treatment. Subsequent re-evaluations will occur every 6 weeks. Patients will continue treatment with all three drugs until tumor progression, or until unacceptable toxicity occurs. If patients experience toxicity caused by gemcitabine/carboplatin and are continuing to benefit from treatment, panitumumab can be continued as a single agent (at the same dose and schedule), at the discretion of the investigator, until disease progression occurs.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Panitumumab/Gemcitabine/Carboplatin

Systemic therapy

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: DRUG

6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Carboplatin

Intervention Type: DRUG

AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Gemcitabine

Intervention Type: DRUG

1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Interventions

Panitumumab

6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Intervention Type: DRUG

Carboplatin

AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Intervention Type: DRUG

Gemcitabine

1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Intervention Type: DRUG

Other Intervention Names

Systemic Therapy; Vectibix; Systemic Therapy; Paraplatin; Systemic Therapy; Gemzar

Eligibility Criteria

Inclusion Criteria

1. Female patients >=18 years of age.

2. Histologically or cytologically confirmed diagnosis of unresectable locally advanced or stage IV breast cancer.

3. No more than 1 prior treatment regimen for metastatic breast cancer.

4. Estrogen receptor and progesterone receptor negative (defined as <10% staining by IHC).

5. Paraffin-embedded tumor tissue (from the primary tumor or metastasis) for biomarker testing. (In the absence of paraffinembedded tissue, unstained paraffin-embedded tumor slides are acceptable).

6. Measurable disease, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines

7. HER2 negative tumors. HER2 negativity must be confirmed by one of the following:

• FISH-negative (FISH ratio <2.2), or
• IHC 0-1+, or
• IHC 2-3+ AND FISH-negative (FISH ratio <2.2)

8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.

9. Absolute neutrophil count (ANC) >=1.5 × 109/L; platelet count >=100 × 109/L; hemoglobin >=9.0 g/dL.

10. Creatinine <=1.5 mg/dL, or creatinine clearance >=40 mL/min (as calculated by the Cockcroft-Gault method, as follows: Female creatinine clearance = (140 - age) × (weight in kg) × 0.85 (serum creatinine × 72)

11. Adequate hepatic function, defined as follows: total bilirubin <=1.5 x ULN; aspartate aminotransferase (AST) <=3 × ULN (or <= 5 x ULN if liver metastases); alanine aminotransferase (ALT) <=3 x ULN (or <=5 x ULN if liver metastases).

12. Magnesium level >= the institutional lower limit of normal (LLN).

13. Women of childbearing potential must agree to use adequate contraception (per institutional standard of care) during treatment and until 6 months after the last administration of investigational products.

Exclusion Criteria

1. Patients with brain metastases are not eligible.

2. History of another primary cancer, with the exception of the following:

• Curatively treated in situ cervical cancer;
• Curatively resected non-melanoma skin cancer;
• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for >=5 years prior to study enrollment.

3. History of interstitial lung disease (e.g., pneumonitis, pulmonary fibrosis), or any evidence of interstitial lung disease on the CT scan of the chest performed at the baseline visit.

4. Prior anti-EGFR antibody therapy (e.g., cetuximab), or treatment with small-molecule EGFR inhibitors (e.g., gefitinib, erlotinib, lapatinib).

5. Radiotherapy <=14 days prior to study enrollment. Any acute effects of radiotherapy must be resolved prior to the administration of study drugs.

6. Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (e.g., bevacizumab) <=21 days prior to study enrollment.

7. Prior therapy with gemcitabine or carboplatin in the metastatic setting is not permitted. Patients who received gemcitabine or carboplatin as part of adjuvant therapy are eligible, as long as recurrence was first documented >12 months after the last exposure to the drug(s).

8. Major surgery within 28 days or minor surgery within 14 days of study enrollment.

9. Requirement of chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine).

10. Any investigational agent or therapy <=30 days prior to study enrollment.

11. Uncontrolled or intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

12. History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with the study participation or administration of the investigational products, or that may interfere with the interpretation of the results.

13. Unwillingness or inability to comply with study requirements.

14. Women who are pregnant or breastfeeding.

15. Patients with known human immunodeficiency virus (HIV), hepatitis C virus, and/or acute or chronic hepatitis B virus infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denise A Yardley, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Los Robles

Thousand Oaks, California, United States

Aventura Hospital and Medical Center

Aventura, Florida, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Providence Medical Group

Terre Haute, Indiana, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

National Capital Clinical Research Consortium

Bethesda, Maryland, United States

St. Louis Cancer Care

Chesterfield, Missouri, United States

Research Medical Center

Kansas City, Missouri, United States

Nebraska Methodist Cancer Center

Omaha, Nebraska, United States

Atlantic Health System

Morristown, New Jersey, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Family Cancer Center

Collierville, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

Texas Health Physician Group

Dallas, Texas, United States

Peninsula Cancer Institute

Newport News, Virginia, United States

Countries

United States

Other Identifiers

SCRI BRE 126

Identifier Type: -

Identifier Source: org_study_id