Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor

Summary: This phase II trial is studying how well CCI-779 works in treating patients with soft tissue sarcoma or gastrointestinal stromal tumor. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop tumor cells from dividing so they stop growing or die.

Detailed description: PRIMARY OBJECTIVES:
  I. To assess the antitumor activity of CCI-779 in this patient population.
  SECONDARY OBJECTIVES:
  I. To assess the following in patients with soft tissue sarcomas and following treatment with CCI-779: duration of response, time to progression, survival.
  TERTIARY OBJECTIVES:
  I. To describe and correlate the following with patient characteristics and outcome in this patient population and following treatment with CCI-779: relative levels of 4EBP1 to eIF4E, phospho 4EBP1, total and phospho ribosomal S6 on pretreatment tumor tissue, expression levels of EGFR, activated EGFR, Her2, c-Myc, phospho Akt, total Akt, phospho-mTOR and total mTOR on pretreatment tumor tissue, drug induced inhibition of p70S6 kinase activity, and phosphorylation of S6 in PBMC, relative levels of serum sirolimus in post-treatment samples.
  OUTLINE:
  Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR.
  Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologic confirmed soft tissue sarcoma
  -  Measurable disease; for patients having only lesions measuring at least 1 cm to less than 2 cm, must use spiral CT imaging for both pre- and post-treatment tumor assessments
  -  Absolute neutrophil count (ANC) >= 1,500/μL
  -  Platelets (PLTS) >= 100,000/μL
  -  Hgb >= 10.0 g/dL
  -  Direct bilirubin =< 1.5 x ULN (upper limit normal)
  -  AST(SGOT) =< 2.5 x ULN or =< 5 x ULN* if liver metastases are present
  -  ALT(SGPT) =< 2.5 x ULN or =< 5 x ULN* if liver metastases are present
  -  Creatinine =< 1.5 x ULN, or if greater, creatinine clearance >= 50 mL/min/1.73 m^2
  -  Baseline glucose levels
  -  Fasting serum cholesterol =< 350 mg/dL (9.0 mmol/L)
  -  Fasting triglycerides =< 400 mg/dL (4.56 mmol/L)
  -  ECOG Performance Status (PS) 0, 1 or 2
  -  Life expectancy >= 12 weeks
  -  Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
  Exclusion Criteria:
  -  Any of the following as this regimen may be harmful to a developing fetus or nursing child:
  -  Pregnant women
  -  Breast-feeding women
  -  Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception ( diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
  -  Any of the following:
  -  Nitrosoureas or mitomycin =< 6 weeks prior to study entry
  -  Other chemotherapy =< 4 weeks prior to study entry
  -  Radiotherapy =< 4 weeks prior to study entry
  -  Concurrent use of any other investigation agent
  -  Adverse events due to agents administered =< 4 weeks prior to study entry
  -  History of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779
  -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, diabetes, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  -  Known HIV-positive patients receiving combination anti-retroviral therapy
  -  Prior chemotherapy for metastatic disease
  -  Exceptions:
  -  Patients with GIST who fail Gleevec are eligible
  -  Patients who have had adjuvant/neoadjuvant chemotherapy are also eligible
  -  Known brain metastases
  -  Exception: Patients with treated brain metastatic disease with stable symptoms after treatment for >= 1 month

Relevance to patient case: not relevant