Sutent + Taxol for Advanced Esophageal Cancer

Study Overview
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Brief Summary
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Paclitaxel is known to be active as a single and combination agent in esophageal cancer, and has also been demonstrated to have anti-angiogenic properties in weekly dosing regimens. Sunitinib malate is an anti-angiogenic drug with the potential to improve responses when combined with chemotherapy, as demonstrated with other regimens in similar settings. We believe that the combination of paclitaxel and sunitinib malate offer great promise in the treatment of advanced esophageal cancer.

Detailed Description
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OUTLINE: This is a multi-center study. Treatment will be administered on an outpatient basis. Chemotherapy will be administered in a 28-day treatment cycle. The 28 days of treatment with paclitaxel and sunitinib malate (plus the time required to recover if toxicity is encountered) is defined as a cycle. Paclitaxel 90 mg/m2 IV on days 1, 8 and 15. Sunitinib malate 37.5 mg orally, daily. After 4 cycles, paclitaxel will be discontinued and patients will continue on sunitinib malate until disease progression, unacceptable toxicity, or physician discretion. Performance Status: ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2 Life expectancy: Not specified Hematopoietic: International Normalized Ratio (INR) < 1.2 Partial Thromboplastin Time (PTT) < 1.5 x Upper Limit of Normal (ULN) Platelets > 100 K/mm3 Hemoglobin > 8 g/dL Absolute Neutrophil Count (ANC) > 1.0 K/mm3 Hepatic: Aspartate transaminase (AST) ≤ 2.5 x ULN, or ≤ 5.0 x ULN if the transaminase elevation is due to known liver metastases. Alanine transaminase (ALT) ≤ 2.5 x ULN, or ≤ 5.0 x ULN if the transaminase elevation is due to known liver metastases. Total bilirubin < 2.0 x ULN Renal: Serum creatinine ≤ 2 x ULN or a calculated creatinine clearance (using Cockcroft-Gault formula) > 50 cc/min Cardiovascular: No history of unstable angina, myocardial infarction, coronary artery bypass grafting surgery within 12 months prior to registration for protocol therapy. Patients may be on anti-anginal medications, but must be stable on those medications for at least 6 months. No history of New York Heart Association class II or greater congestive heart failure. Pulmonary: Not specified

Official Title
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A Phase II Study of Sunitinib Malate (Sutent®) With Paclitaxel (Taxol®) in Patients With Advanced Esophageal Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: Sunitinib malate
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed recurrent or metastatic esophageal or gastro-esophageal junction squamous cell or adenocarcinoma Measurable or evaluable disease per RECIST within 28 days prior to being registered on protocol therapy. No more than one prior chemotherapy regimen for locally advanced or metastatic disease is allowed. Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Age > 18 years. Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for 3 month period thereafter. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. Females must not be breastfeeding. Must be willing to comply with study and follow up procedures. Exclusion Criteria: No history of inadequately controlled hypertension (Systolic Blood Pressure > 150 or Diastolic Blood Pressure > 100) on a standard regimen of antihypertensive therapy. No prior treatment with vascular endothelial growth factor (VEGF) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, or other anti-angiogenic agent. No serious, non-healing wound, ulcer, or bone fracture. No history of or current hemoptysis. No history of transient ischemic attack (TIA) or stroke within 12 months prior to registration for protocol therapy. No evidence of bleeding diathesis, coagulopathy, prolonged INR or PTT. No chronic anti-coagulation treatment. No history of central nervous system or brain metastases. No history of any major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration for protocol therapy, or anticipation of need for major surgical procedure during the course of protocol therapy. No history of any minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to registration for protocol therapy. No history of clinically significant peripheral neuropathy, i.e., Grade > 3 neuromotor or neurosensory toxicity as defined by NCI CTCAE v 3.0. No known history of adrenal insufficiency documented by adrenocorticotropic hormone (ACTH) stimulation testing. No prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec), obtained within 28 days prior to being registered for protocol therapy. No other active cancers No clinically significant infections as judged by the treating investigator. No history of a seizure disorder. No known history of hypersensitivity to paclitaxel. No CYP3A4 inducers and inhibitors allowed within 14 days prior to registration on protocol therapy and while receiving the protocol therapy.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Treatment will be administered on an outpatient basis. Chemotherapy will be administered in a 28-day treatment cycle. The 28 days of treatment with paclitaxel and sunitinib malate (plus the time required to recover if toxicity is encountered) is defined as a cycle. Paclitaxel 90 mg/m2 IV on days 1, 8 and 15. Sunitinib malate 37.5 mg orally, daily. After 4 cycles, paclitaxel will be discontinued and patients will continue on sunitinib malate until disease progression, unacceptable toxicity, or physician discretion. | Drug: Sunitinib malate<br>* Sunitinib malate 37.5 mg orally, daily<br>Drug: Paclitaxel<br>* Paclitaxel 90 mg/m2 IV on days 1, 8 and 15.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Rate at 24 Weeks | To determine the rate of non-progressive disease at 24 weeks from the first dose of the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma, where progression is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | To determine the response rate for the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma per RECIST criteria. | 6 months | 
| Overall Survival | To determine the one year overall survival rate for the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma | 12 months | 
| Progression-Free Survival | To determine the time to progression for the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma per RECIST criteria. | 12 months | 
| Toxicity Profile | Determine the most frequent toxicities associated with the treatment regimen, per the CTCAE version 3 (Common Toxicity Criteria for Adverse Events) criteria. | 16 months |