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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00098501
First received: December 7, 2004
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: pelitinib
Drug: temsirolimus
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Number and severity of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 30 days after last dose of study treatment ] [ Designated as safety issue: Yes ]
    Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.


Secondary Outcome Measures:
  • Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Time from the start of the treatment until disease progression/recurrence, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Time until any treatment related toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Time until hematologic nadirs (white blood cells [WBC], absolute neutrophil count [ANC], platelets) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: October 2004
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: EKB-569
Drug: temsirolimus
Given PO
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098501

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Charles Erlichman Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00098501     History of Changes
Other Study ID Numbers: NCI-2012-01459, MC027C, NCI-6200, MAYO-MC027C, CDR0000398176, U01CA069912
Study First Received: December 7, 2004
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 14, 2014