Open Label Study Of SU011248 In Combination With Trastuzumab For Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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The current study is to evaluate: Overall response rate for the combination of trastuzumab and SU011248 in metastatic or locally recurrent breast cancer; evaluate safety and tolerability of the combination; measure duration of tumor control and survival; assess patient reported outcomes; assess PK in combination with trastuzumab and compare efficacy and safety.

Official Title
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A Phase 2 Efficacy And Safety Study Of SU011248 In Combination With Trastuzumab As Treatment For Metastatic Disease In Patients With Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: SU011248/Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of breast cancer with evidence of 1) unresectable, locally recurrent, or 2) metastatic disease. HER2 positive disease (3+ by immunohistochemistry [IHC] or FISH-positive) Candidate for treatment with trastuzumab. Prior treatment with trastuzumab and or/ lapatinib in the neoadjuvant, adjuvant or metastatic disease setting is permitted. Treatment with hormone therapy in the adjuvant and/or advanced disease setting is permitted. Exclusion Criteria: Prior treatment with >1 regimen of cytotoxic therapy in the advanced disease setting. Adjuvant chemotherapy is permitted Prior exposure to trastuzumab if the patient had developed severe hypersensitivity reactions. Prior treatment on a SU11248 clinical trial. Uncontrolled brain metastases.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: SU011248/Trastuzumab<br>* SU011248 will be administered orally, starting dose of 37.5 mg daily on a continuous regimen. Trastuzumab will be administered weekly (loading dose 4 mg/kg followed by weekly 2mg/kg) or every 3 weeks (loading dose 8 mg/kg followed by 6mg/kg q3w). Study treatment should continue until progression, withdrawal for other reasons, or for up to 18 months following which patients requiring continued access will be offered SU011248 on a separate protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Overall Confirmed Objective Disease Response | Objective disease response =participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target and non-target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions associated to a non-progressive disease response for the non target lesions. | From start of treatment through 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DR) | Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or death due to any cause. If tumor progression data included more than 1 date, the first date was used. DR was calculated as (the end date for DR minus first CR or PR that was subsequently confirmed +1) divided by 7. | From start of treatment through 18 months | 
| Percentage of Participants With Clinical Benefit | Percent of participants with confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST.CR was defined as disappearance of all target and non-target lesions.PR was defined as >=30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions associated to non-progressive disease response for non target lesions.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started. | From start of treatment through 18 months | 
| Progression Free Survival (PFS) | Time from first dose of study treatment to first documentation of objective tumor progression, or to death on-study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS was calculated as (first event date minus first dose date +1) divided by 7. | From start of treatment through 18 months | 
| Time to Progression (TTP) | Time from first dose of study treatment to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP was calculated as (first event date minus first dose date +1) divided by 7. | From start of treatment through 18 months | 
| Overall Survival (OS) | Time from first dose of study treatment to first documentation of death due to any cause. OS was calculated as (date of death minus first dose date +1) divided by 7 * 4.33. | From start of study treatment until death or 2 years from first study treatment | 
| Probability of Survival at One Year | One- year survival probability was estimated using the Kaplan-Meier method. | From start of study treatment until death or 2 years from first study treatment | 
| EORTC QLQ-C30 | EORTC QLQ-C30 scales consist of 30 questions: functional (physical/role/cognitive/emotional/ social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms. | From start of treatment through 18 months | 
| EORTC QLQ (BR23) | BR23: consisted of 23 questions which measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. | From start of treatment through 18 months | 
| Dose-corrected Trough Plasma Concentrations (Ctrough) of Sunitinib | Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg. | Predose on Day 1 of Cycle 3 and 5 | 
| Dose-corrected Ctrough of SU-012662 (Sunitinib's Metabolite) | Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg. | Predose on Day 1 of Cycle 3 and 5 | 
| Dose-corrected Ctrough of Total Drug (Sunitinib + SU-012662) | Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg. | Predose on Day 1 of Cycle 3 and 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer Metastatic