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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00894504
Recruitment Status : Completed
First Posted : May 7, 2009
Results First Posted : December 15, 2014
Last Update Posted : May 15, 2015
Eli Lilly and Company
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Panitumumab Drug: Carboplatin Drug: Gemcitabine Phase 2

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  (Clinical Trial)
Actual Enrollment : 71 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Panitumumab, Gemcitabine, and Carboplatin in Triple-Negative Metastatic Breast Cancer
Study Start Date : February 2010
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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:
  • Systemic Therapy
  • Vectibix

Drug: Carboplatin
AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
Other Names:
  • Systemic Therapy
  • Paraplatin

Drug: Gemcitabine
1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
Other Names:
  • Systemic Therapy
  • Gemzar

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: every 6 weeks until treatment discontinuation ]
    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

Secondary Outcome Measures :
  1. Objective Response Rate and Clinical Benefit Rate [ Time Frame: every 6 weeks until treatment discontinuation ]
    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.

  2. Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity [ Time Frame: every 6 weeks until discontinuation of treatment, expected average of 18 months ]
    Assessments made through analysis of treatment-related adverse events and serious adverse events

  3. 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 [ Time Frame: 18 months ]
    Median PFS (95% CI), months, reported by biomarker expression/mutation status for: EGFR, p53, PTEN, PIK3CA, KRAS

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00894504

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

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00894504     History of Changes
Other Study ID Numbers: SCRI BRE 126
First Posted: May 7, 2009    Key Record Dates
Results First Posted: December 15, 2014
Last Update Posted: May 15, 2015
Last Verified: April 2015

Keywords provided by SCRI Development Innovations, LLC:
Metastatic Breast Cancer
Triple Negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs