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

A Phase II Trial of Panitumumab, Gemcitabine, and Carboplatin in Triple-Negative Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Panitumumab; Drug: Carboplatin; Drug: Gemcitabine

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Thousand Oaks, California, United States, 91360
      • Los Robles
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura Hospital and Medical Center
    • Ft. Myers, Florida, United States
      • Florida Cancer Specialists
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Providence Medical Group
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
    • Bethesda, Maryland, United States, 20817
      • National Capital Clinical Research Consortium
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Louis Cancer Care
    • Kansas, Missouri, United States, 64132
      • Research Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Cancer Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Collierville, Tennessee, United States, 38119
      • Family Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 76011
      • Texas Health Physician Group
  • Virginia
    • Newport News, Virginia, United States, 23601
      • Peninsula Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

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: Panitumumab/Gemcitabine/Carboplatin; Systemic therapy

Drug: Panitumumab; 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks); Other Names: Vectibix; Systemic Therapy; Drug: Carboplatin; AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks); Other Names: Paraplatin; Systemic Therapy; Drug: Gemcitabine; 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks); Other Names: Gemzar; Systemic Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Measured from Day 1 of study drug administration to disease progression - defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a 20% increase in the sum of the longest diameter of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions	every 6 weeks until treatment discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate and Clinical Benefit Rate	Estimated as the proportion of subjects who meet the criteria for complete or partial response (CR or PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 - for target lesions assessed by MRI: Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions.	every 6 weeks until treatment discontinuation
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity	Assessments made through analysis of treatment-related adverse events and serious adverse events	every 6 weeks until discontinuation of treatment, expected average of 18 months
Correlation of Biomarker Expressions of EGFR, K-ras, p53, PTEN Expression, and PI3K in Triple-negative Breast Cancer With Response to Treatment With the Combination of Gemcitabine, Carboplatin, and Panitumumab	Median PFS (95% CI), months, reported by biomarker expression/mutation status for: EGFR, p53, PTEN, PIK3CA, KRAS	18 months

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Eli Lilly and Company; Amgen

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: May 5, 2009
• First Submitted That Met QC Criteria: May 6, 2009
• First Posted (Estimate): May 7, 2009

Study Record Updates

• Last Update Posted (Estimate): May 15, 2015
• Last Update Submitted That Met QC Criteria: April 28, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Gemcitabine; Gemzar; Carboplatin; Triple Negative; Metastatic Breast Cancer; Panitumumab; Vectibix
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Gemcitabine; Carboplatin; Panitumumab
• Other Study ID Numbers: SCRI BRE 126