MK-0646, Etoposide, and Cisplatin in Treating Patients With Extensive-Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00869752
First received: March 25, 2009
Last updated: March 6, 2014
Last verified: July 2012
  Purpose

RATIONALE: Monoclonal antibodies, such as MK-0646, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of MK-0646 when given together with etoposide and cisplatin and to see how well it works in treating patients with extensive-stage small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: anti-IGF-1R recombinant monoclonal antibody MK-0646
Drug: cisplatin
Drug: etoposide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Trial of MK-0646, a Monoclonal Antibody Against Insulin-Like Growth Factor-1 Receptor, in Combination With Etoposide and Cisplatin in Extensive Stage Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Recommended phase II dose of MK-0646 in combination with standard etoposide and cisplatin chemotherapy [ Time Frame: Each dose level ] [ Designated as safety issue: No ]
    Evaluate safety, tolerability in combination with standard chemotherapy.

  • Toxicity and tolerability according to NCI CTCAE v3.0 [ Time Frame: Phase 1, each dose level and Phase II ] [ Designated as safety issue: Yes ]
    Look at toxicity and tolerability of MK0646 in combination with standard therapy.

  • Preliminary efficacy [ Time Frame: Phase 1 dose levels, evey other cycle ] [ Designated as safety issue: No ]
    Look for evidence of response

  • Objective response rate [ Time Frame: Phase II portion, every other cycle ] [ Designated as safety issue: No ]
    Determine objective response rate including complete response rate, progression free survival and overall survival.

  • Predictive and prognostic impact of biomarkers [ Time Frame: Each cycle ] [ Designated as safety issue: No ]
    Blood samples will be collected and analyzed for occurrence of human-anti-humanized antibody response to MK0646 as well as IGF-1R analysis.


Enrollment: 12
Study Start Date: January 2009
Study Completion Date: July 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
MK-0646, a monoclonial antibody in combination with etoposide and cisplatin.
Biological: anti-IGF-1R recombinant monoclonal antibody MK-0646
MK-0646 should be given 1st followed within 30-60 minutes by cisplatin and then etoposide for cycles which include both MK-0646 and chemotherapy. Cycles are 21 days
Drug: cisplatin
MK-0646 should be given 1st followed within 30-60 minutes by cisplatin and then etoposide for cycles which include both MK-0646 and chemotherapy. Cycles are 21 days
Drug: etoposide
MK-0646 should be given 1st followed within 30-60 minutes by cisplatin and then etoposide for cycles which include both MK-0646 and chemotherapy. Cycles are 21 days

Detailed Description:

OBJECTIVES:

  • To determine the recommended phase II dose of MK-0646 in combination with a standard etoposide and cisplatin chemotherapy regimen in patients with extensive stage small cell lung cancer. (phase I)
  • To assess the toxicity and tolerability of this regimen in these patients. (phases I and II)
  • To evaluate the preliminary efficacy of this regimen in these patients. (phase I)
  • To assess the efficacy of this regimen, in terms of objective response rate, as well as complete response rate in these patients. (phase II)
  • To assess progression-free survival and overall survival of patients treated with this regimen. (phase II)
  • To explore the predictive and prognostic impact of biomarkers in patients treated with this regimen. (phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of MK-0646 followed by a phase II study.

Patients receive MK-0646 IV over 1 hour on days 1, 8, and 15 and cisplatin IV and etoposide IV once daily on days 1-3. Treatment repeats every 3 weeks for 4 to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients with complete response (CR) or partial response (PR) may continue MK-0646 in the absence of disease progression, with temporary discontinuation while undergoing prophylactic cranial irradiation or thoracic radiotherapy.

Blood samples are collected at baseline (pre-dose) and periodically for biomarker and pharmacogenetic correlative studies. Blood samples are analyzed for changes in expression of IGF biomarkers (e.g., IGF-1, IGF-2 and IGF-PB), haplotype tagging analysis of the IGF-1R, and evaluation of the immunoglobulin G fragment C receptor polymorphisms.

After completion of study therapy, patients are followed at 4 weeks. Patients with responding disease (i.e., CR, PR, or stable disease) are followed every 3 months until relapse or progression.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed small cell lung cancer (SCLC)

    • Extensive stage disease that is incurable but amenable to treatment with platinum-based chemotherapy
    • Small cell and variant histologies allowed
    • No mixed tumors (i.e., small and large cell) or other neuroendocrine tumors of the lung
  • Clinically and/or radiologically documented measurable disease, defined as ≥ 1 unidimensionally measurable site of disease ≥ 20 mm by chest x-ray, ≥ 15 mm by CT scan (lymph nodes), or ≥ 10 mm by CT scan or physical exam
  • No uncontrolled or symptomatic CNS metastases

    • Patients who have completed radiotherapy or have undergone complete resection of CNS metastases are allowed provided they are on stable (non-increasing) or decreasing doses of corticosteroids

PATIENT CHARACTERISTICS:

  • Life expectancy ≥ 12 weeks
  • ECOG performance status 0-2
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin ≤ upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN (≤ 5 times ULN if documented liver metastases)
  • Serum creatinine ≤ ULN OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or lactating
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy
  • No other active cancer
  • No untreated and/or uncontrolled cardiovascular or other comorbid conditions

    • Patients with a significant cardiac history, even if controlled, should have a LVEF > 50%
  • No uncontrolled diabetes
  • Must be accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior cytotoxic chemotherapy or other IGF-1R targeting agents for SCLC
  • At least 3 weeks since prior radiotherapy to neurological sites
  • No prior radiotherapy to the lungs
  • Prior surgery allowed provided that wound healing has occurred

    • At least 14 days since prior major surgery
  • No other concurrent investigational agents or therapy
  • No other concurrent anticancer treatment
  • No concurrent radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869752

Locations
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Peter Ellis, MD Margaret and Charles Juravinski Cancer Centre
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00869752     History of Changes
Other Study ID Numbers: I190, CAN-NCIC-IND190, CDR0000634447
Study First Received: March 25, 2009
Last Updated: March 6, 2014
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
combined type small cell lung cancer
fusiform type small cell lung cancer
polygonal type small cell lung cancer
lymphocyte-like type small cell lung cancer
extensive stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Etoposide phosphate
Cisplatin
Etoposide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 24, 2014