CCI-779 in Treating Patients With Stage IIIB (With Pleural Effusion) or Stage IV Non-Small Cell Lung Cancer

A Phase II Study of the mTOR Inhibitor, CCI-779 in Patients With Advanced Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: temsirolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22.	Other: laboratory biomarker analysis; Correlative studies; Drug: temsirolimus; Given IV; Other Names: Torisel; CCI-779; cell cycle inhibitor 779

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST)	Confidence intervals for the true success proportion will be calculated using the Duffy-Santner approach.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival time	Estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 5 years
Time to disease progression	Estimated using the method of Kaplan-Meier.	Time from registration to documentation of disease progression, assessed up to 5 years
Progression-free survival	Computed and binomial confidence intervals for the true success proportion will be calculated.	24 weeks
Effects of CCI-779 on mTOR as assessed by expression of 4EBP, phosphoAkt, p70S6kinase, eIF4E, cyclinD1, Her2, and EGFR		Day 8

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Alex Adjei, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 9, 2004
• First Posted (Estimate): March 10, 2004

Study Record Updates

• Last Update Posted (Estimate): July 16, 2013
• Last Update Submitted That Met QC Criteria: July 15, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: NCI-2012-01810; U10CA025224 (U.S. NIH Grant/Contract); N0323; CDR0000355117; NCCTG-N0323