Clinical trial NCT00087074: CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor
Official title: A Trial of CCI-779 in Patients With Soft Tissue Sarcoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor
Recurrent Adult Soft Tissue Sarcoma
Stage I Adult Soft Tissue Sarcoma
Stage II Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-07-12
Enrollment: 55
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 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 criteria: 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

Primary outcomes:
measure: Proportion of confirmed tumor responses, defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart
timeFrame: Up to 6 months (6 courses)
Secondary outcomes:
measure: Survival time
timeFrame: Time from registration to death due to any cause, assessed up to 5 years
measure: Time to disease progression
timeFrame: Time from registration to documentation of disease progression, assessed up to 5 years
measure: Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented
timeFrame: Up to 5 years
measure: Time to treatment failure
timeFrame: Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Scott Okuno
role: PRINCIPAL_INVESTIGATOR
References: