PhII ICb With/Without Erbitux in MBC Pts

Study Overview
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Brief Summary
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The purpose of this study is to determine the objective response rates produced by irinotecan and carboplatin therapy with or without Erbitux in patients with Metastatic Breast Cancer.

Official Title
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Randomized Phase II Study of Weekly Irinotecan/Carboplatin (ICb) With or Without Cetuximab (Erbitux) in Patients With Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Irinotecan + Carboplatin
* Drug: irinotecan + Carboplatin + erbitux


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Male and female patients will be eligible for inclusion in this study if they meet all of the following criteria: Has cytologically or pathologically confirmed, breast cancer with documented HER2+ (positive) (3+ by IHC or FISH+) or HER2- (negative) disease. ER, PR, and HER2 status must be documented in the electronic Case Report Form (eCRF) NOTE: Patients whose breast cancers are HER2 (2+) by IHC must undergo FISH testing to confirm HER2+ (positive) status. Has clinically confirmed Stage IV metastatic breast cancer (MBC) Has undergone prior Herceptin therapy if breast cancer is HER2+ (positive) Has measurable MBC as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria NOTE: Ascites, pleural effusion, and bone metastases are not considered measurable. Has had up to 1 prior chemotherapy regimens for metastatic disease. Previously untreated disease is permitted. Has had no prior treatment with irinotecan, carboplatin, or cisplatin Has an ECOG Performance Status (PS) 0-2 Is greater than 18 years of age Please see protocol for specific details regarding appropriate laboratory values for inclusion to the study. Any prior radiation therapy has been completed > 2 weeks prior to the start of study treatment NOTE: Previously irradiated lesions will not be evaluable; however, these patients will still be eligible. Patients must have at least 1 measurable lesion at baseline. Has had a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential). A pregnancy test is also required within 7 days of Dose 1. If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 6 months thereafter. Has signed a Patient Informed Consent Form Has signed a Patient Authorization Form (HIPAA) Has paraffin-embedded breast cancer tissue (either paraffin blocks or 20 unstained slides) available for analysis of EGFR, cytokeratin, and other biological markers. These samples will be sent to the Molecular Profiling Institute (MPI; see Appendix VII). NOTE: Availability of samples should be confirmed prior to randomization (at latest, prior to first dose). EXCLUSION CRITERIA: Has Stage I-III breast cancer or nonmeasurable metastatic breast cancer, or any disease other than that described in inclusion criterion #1 Has received prior treatment with irinotecan, carboplatin, or cisplatin Is receiving any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s) Has received prior therapy which specifically and directly targets the EGFR pathway. Prior Herceptin is required for HER2+ patients. Has had prior severe infusion reaction to a monoclonal antibody Has received organ allograft(s) other than corneal, bone, or skin Has clinically significant uncontrolled cardiac disease (eg, congestive heart failure, symptomatic coronary artery disease or cardiac arrhythmias not well-controlled with medication) or has had a myocardial infarction < 12 months Has ongoing peripheral neuropathy > Grade I Has evidence of symptomatic or untreated central nervous system (CNS) metastases (unless CNS metastases have been irradiated). Chronic steroid treatment for the treatment of CNS metastases must have been discontinued for greater than 4 weeks prior to study enrollment. Has any other significant comorbidity that, in the opinion of the clinical investigator, might compromise any aspect of the study Has active or uncontrolled infection Has acute hepatitis or is known to be HIV positive Has a history of other malignancy within the last 5 years which could affect the diagnosis or assessment of MBC, with the exception of carcinoma of the cervix in situ, carcinoma of the bladder in situ, and basal cell carcinoma Has previously completed a chemotherapy regimen within 3 weeks prior to the start of study treatment, or has related toxicities unresolved prior to the start of study treatment NOTE: If patient was receiving prior weekly or daily chemotherapy, he/she may begin study therapy 2 weeks after stopping prior therapy provided all toxicities have resolved; peripheral neuropathy must be less than Grade I as per exclusion criterion #8 above. Has had major surgery within 3 weeks from the start of study treatment, without complete recovery Has participated in any investigational drug study within 4 weeks preceding the start of study treatment Has received a concurrent immunotherapy or hormonal anticancer agent within 2 weeks prior to the start of the study treatment Is receiving a tyrosine kinase inhibitor (ie, IressaTM) Has had any prior stem cell or bone marrow transplant for any prior hematologic malignancy Is pregnant or lactating Is unable to comply with the requirements of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>irinotecan 90 mg/m2 and carboplatin AUC=2.0 on Days 1 and 8 of each 21-day cycle (Arm 1, ICb) | Drug: Irinotecan + Carboplatin<br>* irinotecan 90 mg/m2 and carboplatin AUC=2.0 on Days 1 and 8 of each 21-day cycle<br>|
| Experimental: Arm 2<br>irinotecan 90mg/m2, carboplatin AUC=2.0 on Days 1 and 8 of each 21- day cycle plus Erbitux 400 mg/m2 Week 1 and then 250 mg/m2 weekly thereafter, (Arm 2, ICb+Erbitux) | Drug: irinotecan + Carboplatin + erbitux<br>* irinotecan 90mg/m2, carboplatin AUC=2.0 on Days 1 and 8 of each 21- day cycle plus Erbitux 400 mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rates (ORR) | To determine the objective response rates (CR + PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. | From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 60 months. | 
| Median Time of Progression-free Survival (PFS) | PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. | 2 years | 
| Median Overall Survival (OS) | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. | 2 years |