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

Gastrointestinal Stromal Tumor Clinical Trial

Official title:

A Trial of CCI-779 in Patients With Soft Tissue Sarcoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00087074
• Other study ID #: NCI-2012-02809
• Secondary ID: MC027BN01CM17104
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2004
• Last updated: June 3, 2013
• Start date: June 2004

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors
• Recurrent Adult Soft Tissue Sarcoma
• 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

Intervention

Drug:
• temsirolimus
Given IV

Other:
• laboratory biomarker analysis
Optional correlative studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Up to 6 months (6 courses)	No
Secondary	Survival time	The distribution of survival time will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 5 years	No
Secondary	Time to disease progression	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from registration to documentation of disease progression, assessed up to 5 years	No
Secondary	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		Up to 5 years	No
Secondary	Time to treatment failure		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	No