CCI-779 and EKB-569 in Treating Patients With Advanced Solid Tumors

A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors

This phase I trial is studying the side effects, best way to give, and best dose of CCI-779 and EKB-569 in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. EKB-569 may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving CCI-779 together with EKB-569 may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: pelitinib; Drug: temsirolimus

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of the combination of CCI-779 and EKB-569 in patients with advanced solid tumors.

II. Determine the toxicity of this regimen in these patients. III. Determine the response rate in patients treated with this regimen.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 treatment groups.

Group I: Patients receive oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21.

Cohorts of 3-6 patients receive escalating doses of EKB-569 and CCI-779 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Group II: Patients receive oral EKB-569 at the MTD on days 4-28 of course 1 and days 1-28 of all subsequent courses and CCI-779 at the MTD on days 1-3 and 15-17.

Group III: Patients receive EKB-569 at the MTD as in group I and oral CCI-779 at the MTD on days 7-9 and 19-21 of course 1 and days 1-3 and 15-17 of all subsequent courses.

In all groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30-42 patients (18-30 for group I, 6 for group II, and 6 for group III) will be accrued for this study within 1.35-1.75 years.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

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 confirmed unresectable solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy
• No CNS 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 normal
• AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver involvement)
• Creatinine ≤ 1.5 times ULN
• No New York Heart Association class III or IV heart disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• Fasting cholesterol < 350 mg/dL
• Fasting triglycerides < 400 mg/dL
• No uncontrolled infection
• No seizure disorder
• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent immunotherapy
• No concurrent prophylactic colony-stimulating factor therapy
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy
• No concurrent oral contraceptives
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to > 30% of bone marrow
• No concurrent radiotherapy
• More than 7 days since prior CYP3A4 inducers
• No prior mTOR-targeting agents
• No prior epidermal growth factor receptor-targeting agents
• No concurrent antiretroviral therapy that induces or inhibits CYP3A4 for HIV-positive patients
• No other concurrent investigational agents
• No concurrent warfarin

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 oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21.	Drug: pelitinib; Other Names: EKB-569; Drug: temsirolimus; Given PO; Other Names: Torisel; CCI-779; cell cycle inhibitor 779

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients		Up to 28 days
Number and severity of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0	Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.	Up to 30 days after last dose of study treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression	Up to 3 years
Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST)	Time from the start of the treatment until disease progression/recurrence, assessed up to 3 years
Time until any treatment related toxicity	Up to 3 years
Time until treatment related grade 3+ toxicity	Up to 3 years
Time until hematologic nadirs (white blood cells [WBC], absolute neutrophil count [ANC], platelets)	Up to 3 years
Time to treatment failure	Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: December 7, 2004
• First Submitted That Met QC Criteria: December 7, 2004
• First Posted (Estimate): December 8, 2004

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus; EKB 569
• Other Study ID Numbers: NCI-2012-01459; U01CA069912 (U.S. NIH Grant/Contract); MC027C; NCI-6200; MAYO-MC027C; CDR0000398176