Clinical trial NCT00730353: Sutent + Taxol for Advanced Esophageal Cancer
Official title: A Phase II Study of Sunitinib Malate (Sutent®) With Paclitaxel (Taxol®) in Patients With Advanced Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2008-08-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival Rate at 24 Weeks
timeFrame: 24 weeks
Secondary outcomes:
measure: Response Rate
timeFrame: 6 months
measure: Overall Survival
timeFrame: 12 months
measure: Progression-Free Survival
timeFrame: 12 months
measure: Toxicity Profile
timeFrame: 16 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush-Presbyterian St. Luke's Medical Center
state: Illinois
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Bloomington
country: United States
facility: Cancer Care Center of Southern Indiana
state: Indiana
city: Evansville
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: IN Onc/Hem Associates
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Arnett Cancer Care
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: Munster
country: United States
facility: Monroe Medical Associates
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Cleveland
country: United States
facility: Ireland Cancer Center - University Hospitals of Cleveland
state: Ohio
Study officials:
affiliation: Hoosier Cancer Research Network
name: Nasser Hanna, M.D.
role: STUDY_CHAIR
References:
citation: Schmitt JM, Sommers SR, Fisher W, Ansari R, Robin E, Koneru K, McClean J, Liu Z, Tong Y, Hanna N. Sunitinib plus paclitaxel in patients with advanced esophageal cancer: a phase II study from the Hoosier Oncology Group. J Thorac Oncol. 2012 Apr;7(4):760-3. doi: 10.1097/JTO.0b013e31824abc7c.