Clinical trial NCT00474994: Sunitinib in Treating Patients With Metastatic, Locally Advanced, or Locally Recurrent Sarcomas
Official title: A Multicenter Phase II Study of Continuous Dosing of Sunitinib (Sutent®, SU11248) in Non-GIST Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Malignant Fibrous Histiocytoma of Bone
Desmoid Tumor
Endometrial Cancer
Ovarian Cancer
Sarcoma
Small Intestine Cancer
Keywords: chondrosarcoma
recurrent osteosarcoma
localized adult malignant fibrous histiocytoma of bone
metastatic adult malignant fibrous histiocytoma of bone
recurrent adult malignant fibrous histiocytoma of bone
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Kaposi sarcoma
recurrent uterine sarcoma
adult leiomyosarcoma
adult malignant fibrous histiocytoma
adult rhabdomyosarcoma
dermatofibrosarcoma protuberans
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
ovarian sarcoma
uterine leiomyosarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
desmoid tumor
adult angiosarcoma
recurrent adult soft tissue sarcoma
uterine carcinosarcoma
endometrial stromal sarcoma
fibrosarcomatous osteosarcoma
chondrosarcomatous osteosarcoma
adult alveolar soft-part sarcoma
adult epithelioid sarcoma
adult extraskeletal chondrosarcoma
adult extraskeletal osteosarcoma
adult fibrosarcoma
adult malignant hemangiopericytoma
adult malignant mesenchymoma
adult neurofibrosarcoma
adult synovial sarcoma
adult desmoplastic small round cell tumor
adult liposarcoma
anaplastic osteosarcoma
mixed osteosarcoma
small intestine leiomyosarcoma
osteoblastic osteosarcoma
telangiectatic osteosarcoma
classic Kaposi sarcoma
immunosuppressive treatment related Kaposi sarcoma
AIDS-related Kaposi sarcoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Dana-Farber Cancer Institute
First posted: 2007-05-17
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Objective Response
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Mary L. Keohan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Robert Maki, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 nongastrointestinal stromal tumor sarcomas. J Clin Oncol. 2009 Jul 1;27(19):3154-60. doi: 10.1200/JCO.2008.20.9890. Epub 2009 May 18.