Clinical trial NCT00400569: Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma
Official title: Phase II Open-Label Study of Sunitinib Malate (SU011248) in Adult Patients With Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liposarcoma
Leiomyosarcoma
Fibrosarcoma
Malignant Fibrous Histiocytoma
Keywords: Sunitinib malate
SUTENT
SU011248
Soft tissue sarcoma
Gastrointestinal stromal tumors (GIST)
MFH
Tyrosine kinase inhibitor
Imatinib mesylate
Phase II
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2006-11-17
Enrollment: 48
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: This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity.

All patients with unresectable or metastatic soft tissue sarcoma (STS): leiomyosarcoma, liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH) seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study.

Detailed description: This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate, an oral multi-kinase inhibitor. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity which in the opinion of the treating physician or the trial Principal Investigator (PI) compromises the ability of the patient to receive treatment or the patient desires to stop treatment.

All patients with unresectable or metastatic STS: leiomyosarcoma, liposarcoma, fibrosarcoma, and MFH seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study.

An office visit will be required before the beginning of every cycle every 6 weeks to assess toxicity and for physical examination. Complete blood count (CBC) and differential, comprehensive metabolic panel, and electrocardiogram (ECG) will be obtained at every scheduled visit.

Eligibility criteria: Inclusion Criteria:

* Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 grade less than or equal to 1.
* Adequate organ function as defined by the following criteria:

  * Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or equal to 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy
  * Total serum bilirubin less than or equal to 1.5 x ULN
  * Absolute neutrophil count (ANC) greater than or equal to1500/microL
  * Platelets greater than or equal to 100,000/microL
  * Hemoglobin greater than or equal to 9.0 g/dL
  * Serum calcium less than or equal to 12.0 mg/dL
  * Serum creatinine less than or equal to 1.5 x ULN
* Histologically-proven liposarcoma, leiomyosarcoma, fibrosarcoma, or MFH
* Measurable disease radiographically
* Disease that is deemed surgically unresectable and/or metastatic
* Age greater than or equal to 18 years
* Life expectancy greater than 16 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
* Patients may have had up to 3 prior chemotherapies within 4 weeks of starting the study treatment.

Exclusion Criteria:

* Major surgery or radiation therapy or chemotherapy within 4 weeks of starting the study treatment.
* NCI CTCAE version 3 grade 3 hemorrhage within 4 weeks of starting the study treatment.
* History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease.
* Any of the following within the 6 months prior to study drug administration:

  * myocardial infarction,
  * severe/unstable angina,
  * coronary/peripheral artery bypass graft,
  * symptomatic congestive heart failure,
  * cerebrovascular accident or transient ischemic attack, or pulmonary embolism
* Ongoing cardiac dysrhythmias of NCI CTCAE greater than or equal to grade 2
* Prolonged QTc interval on baseline electrocardiogram (ECG) \> 500 msec.
* Hypertension that cannot be controlled by medications (\>150/100 mm Hg despite optimal medical therapy)
* Prior tyrosine kinase inhibitor therapy
* Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
* Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
* Concurrent treatment on another clinical trial, except supportive care or non-treatment trials
* Concomitant use of agents known to induce or inhibit CYP3A4
* Concomitant use of agents metabolized by the cytochrome P450 system
* Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg by mouth \[PO\] daily for thrombo-prophylaxis is allowed)
* Pregnancy or breastfeeding patients
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.

Primary outcomes:
measure: Number of Participants With Overall Response (OR)
timeFrame: From On Treatment to Off Study - average of 6 months
Secondary outcomes:
measure: Participants' Progression Free Survival (PFS)
timeFrame: From On Treatment to Off Study - average of 6 months
measure: Participants' Overall Survival (OS)
timeFrame: From On Treatment to Off Study - average of 6 months
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: 4 years, 7 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Alberto Chiappori, M.D.
role: PRINCIPAL_INVESTIGATOR
References: