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

Pfizer60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Neoplasms

Interventions

SU011248/TrastuzumabDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (27)

Pfizer Investigational Site

Outcomes

Primary Outcomes

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.

Time frame: From start of treatment through 18 months

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Montgomery, Alabama, United States

Pfizer Investigational Site

Newark, Delaware, United States

Pfizer Investigational Site

Newark, Delaware, United States

Pfizer Investigational Site

Wilmington, Delaware, United States

Pfizer Investigational Site

Fort Lauderdale, Florida, United States

Pfizer Investigational Site

Harvey, Illinois, United States

Pfizer Investigational Site

Tinley Park, Illinois, United States

Pfizer Investigational Site

Munster, Indiana, United States

Pfizer Investigational Site

Lafayette, Louisiana, United States

Pfizer Investigational Site

New Iberia, Louisiana, United States

...and 17 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Predose on Day 1 of Cycle 3 and 5