Clinical trial NCT00079235: CCI-779 in Treating Patients With Stage IIIB (With Pleural Effusion) or Stage IV Non-Small Cell Lung Cancer
Official title: A Phase II Study of the mTOR Inhibitor, CCI-779 in Patients With Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-03-10
Enrollment: 50
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 stage IIIB non small cell lung cancer (with pleural effusion) or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop tumor cells from dividing so they stop growing or die. CCI-779 may also stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed description: OBJECTIVES: Primary I. Determine the response rate in patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer treated with CCI-779.

II. Determine the clinical toxic effects of this drug in these patients.

Secondary I. Determine the 24-week progression-free survival rate in patients treated with this drug.

II. Determine the time to progression and overall survival of patients treated with this drug.

III. Evaluate predictive markers of activity (e.g., PTEN mutations and phosphoAkt expression) of this drug in these patients.

OUTLINE: This is a multicenter study.

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 are followed every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 25-55 patients will be accrued for this study within 12 months.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  * Stage IIIB (with pleural effusion) or IV disease
* Measurable disease

  * At least 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
  * The following are not considered measurable disease:

    * Bone lesions
    * Leptomeningeal disease
    * Ascites
    * Pleural/pericardial effusion
    * Inflammatory breast disease
    * Lymphangitis cutis/pulmonis
    * Cystic lesions
    * Abdominal masses that are not confirmed and followed by imaging techniques
* Blood and tissue blocks available
* Must have accessible tumor (i.e., superficial lesions such as lymph node, subcutaneous nodules) to provide core needle biopsy tissue before and during study treatment
* No known brain metastases
* Performance status - ECOG 0-2
* At least 12 weeks
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 10 g/dL
* Bilirubin ≤ 2 times upper limit of normal (ULN)
* AST ≤ 3 times ULN (5 times ULN if hepatic metastases are present)
* Creatinine ≤ 1.5 times ULN
* Serum fasting cholesterol ≤ 350 mg/dL
* Serum fasting triglycerides ≤ 400 mg/dL
* HIV negative
* No uncontrolled infection
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or non-invasive carcinomas
* No concurrent severe underlying disease that would preclude study participation
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after study treatment
* No prior biologic therapy
* No prior gene therapy
* No prior immunotherapy
* No concurrent immunotherapy
* No concurrent prophylactic growth factors to support neutrophil count
* No prior chemotherapy for NSCLC except low-dose cisplatin as a radiosensitizer
* No other concurrent chemotherapy
* No concurrent dexamethasone (10 mg IV)
* No prior radiotherapy to 30% or more of bone marrow
* Concurrent radiotherapy for underlying malignancy and non-target sites (e.g., painful pre-existing bony metastasis) allowed
* No other concurrent investigational therapy
* No concurrent immunosuppressive therapy

Primary outcomes:
measure: Confirmed tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: 24 weeks
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: Effects of CCI-779 on mTOR as assessed by expression of 4EBP, phosphoAkt, p70S6kinase, eIF4E, cyclinD1, Her2, and EGFR
timeFrame: Day 8
Other outcomes:
Locations:
city: Rochester
country: United States
facility: North Central Cancer Treatment Group
state: Minnesota
Study officials:
affiliation: North Central Cancer Treatment Group
name: Alex Adjei
role: PRINCIPAL_INVESTIGATOR
References: