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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00894504
• Other study ID #: SCRI BRE 126
• Status: Completed
• Phase: Phase 2
• First received: May 5, 2009
• Last updated: April 28, 2015
• Start date: February 2010
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Panitumumab
6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
• Carboplatin
AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
• Gemcitabine
1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)

Locations

Country	Name	City	State
United States	Aventura Hospital and Medical Center	Aventura	Florida
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	National Capital Clinical Research Consortium	Bethesda	Maryland
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	St. Louis Cancer Care	Chesterfield	Missouri
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Family Cancer Center	Collierville	Tennessee
United States	Texas Health Physician Group	Dallas	Texas
United States	Florida Cancer Specialists	Ft. Myers	Florida
United States	Research Medical Center	Kansas	Missouri
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Atlantic Health System	Morristown	New Jersey
United States	Tennessee Oncology	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Nebraska Methodist Cancer Center	Omaha	Nebraska
United States	Providence Medical Group	Terre Haute	Indiana
United States	Los Robles	Thousand Oaks	California

Sponsors (3)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Amgen, Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No