Sunitinib in Treating Patients With Metastatic, Locally Advanced, or Locally Recurrent Sarcomas

Ovarian Cancer Clinical Trial

Official title:

A Multicenter Phase II Study of Continuous Dosing of Sunitinib (Sutent®, SU11248) in Non-GIST Sarcomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00474994
• Other study ID #: 07-054
• Secondary ID: P30CA008748MSKCC
• Status: Completed
• Phase: Phase 2
• First received: May 16, 2007
• Last updated: December 15, 2015
• Start date: April 2007
• Est. completion date: November 2010

Study information

• Verified date: December 2015
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with metastatic, locally advanced, or locally recurrent sarcomas.

Description:

OBJECTIVES:

Primary

• Determine the response rate (complete response and partial response) in patients with metastatic, locally advanced, or locally recurrent non-gastrointestinal stromal tumor sarcomas treated with sunitinib malate.

Secondary

• Determine the 16- and 24-week progression-free survival rate (complete response, partial response, and stable disease) in patients treated with this drug.

• Determine the overall survival in patients treated with this drug.

• Correlate clinical response with changes in soluble angiogenesis mediator levels in patients treated with this drug.

• Determine the tumor maximum standardized uptake values by fludeoxyglucose F 18-PET scan in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified by neoplastic subtype (vascular connective tissue neoplasms, leiomyosarcoma, dermatofibrosarcoma protuberans, chordoma, or desmoid tumors vs high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)], or other nongastrointestinal connective tissue tumors [including carcinosarcomas]).

Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed connective tissue neoplasm, including any of the following neoplastic subtypes:

• Vascular connective tissue neoplasms

• Leiomyosarcoma

• Dermatofibrosarcoma protuberans

• Chordoma

• Desmoid tumors

• High-grade undifferentiated pleomorphic sarcoma (e.g., malignant fibrous histiocytoma [including myxofibrosarcoma])

• Carcinosarcomas (e.g., malignant mixed Müllerian tumors)

• Giant hemangiomata

• Kaposi sarcoma

• Metastatic, locally advanced, or locally recurrent disease

• Measurable disease

• Tumor lesions in a previously irradiated area may be considered measurable provided there is evidence of growth that cannot be attributed to necrosis or bleeding

• No gastrointestinal stromal tumor sarcomas

• Prior standard neoadjuvant or adjuvant systemic therapy required for patients with the following diagnoses:

• Rhabdomyosarcoma

• Osteosarcoma

• Ewing sarcoma

• No untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as documented on screening CT scan or MRI

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• Bilirubin = 1.5 mg/dL

• PT and INR = 1.5

• AST and ALT = 2.5 times upper limit of normal

• Creatinine = 1.5 mg/dL

• Calcium = 12 mg/dL

• Blood glucose < 150 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study therapy

• Other malignancies allowed provided sarcoma is the primary disease requiring systemic therapy

• Able to swallow oral medications

• No other disease or illness within the past 6 months, including any of the following:

• Myocardial infarction

• Severe or unstable angina

• Coronary or peripheral artery bypass graft

• Symptomatic congestive heart failure

• Cerebrovascular accident or transient ischemic attack

• Pulmonary embolism

• No evidence of a bleeding diathesis

• No ongoing cardiac dysrhythmias > grade 2

• No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy

• Left ventricular ejection fraction = 50% by echocardiogram or MUGA scan

• No psychiatric illness or social situation that would preclude study compliance

• No pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication

• No prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline EKG

• No hemorrhage = grade 3 in the past 4 weeks

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• No prior sunitinib malate

• No more than 3 prior cytotoxic chemotherapy regimens for metastatic disease

• Adjuvant chemotherapy for sarcoma completed > 1 year prior to study entry is not considered a line of prior treatment

• At least 2 weeks since prior cytotoxic chemotherapy

• At least 6 weeks since prior carmustine or mitomycin C

• At least 1 week since prior biological therapy or small molecule kinase inhibitors

• At least 3 weeks since prior radiotherapy (except for palliative radiotherapy to specific sites)

• Prior palliative radiotherapy allowed provided it is considered medically necessary and there are other target lesions to assess

• More than 4 weeks since prior major surgery

• Concurrent major surgery allowed provided study drug is stopped 2 weeks before surgery and resumed 2 weeks after surgery

• Concurrent palliative radiotherapy (e.g., focal radiotherapy to a bony metastasis for relieving bone pain) allowed

• No other concurrent investigational drugs

• No concurrent participation in another clinical trial

• No concurrent therapeutic anticoagulation (e.g., warfarin)

• Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided requirements for PT and INR are met

• No other concurrent approved or investigational anticancer agents or treatment, including chemotherapy, biological response modifier therapy, hormonal therapy, or immunotherapy

• Concurrent hormone replacement therapy for adrenal insufficiency allowed

• No concurrent antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)

• No concurrent rifampin, theophylline, ketoconazole, or Hypericum perforatum (St. John's wort)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Malignant Fibrous Histiocytoma of Bone
• Desmoid Tumor
• Endometrial Cancer
• Histiocytoma
• Histiocytoma, Malignant Fibrous
• Ovarian Cancer
• Sarcoma
• Small Intestine Cancer

Intervention

Drug:
• sunitinib malate

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Dana-Farber Cancer Institute, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

George S, Merriam P, Maki RG, Van den Abbeele AD, Yap JT, Akhurst T, Harmon DC, Bhuchar G, O'Mara MM, D'Adamo DR, Morgan J, Schwartz GK, Wagner AJ, Butrynski JE, Demetri GD, Keohan ML. Multicenter phase II trial of sunitinib in the treatment of nongastroi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Objective Response	as assessed by RECIST criteria	2 years	No