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
18 Years
N/A
Both
Lung Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Recommended phase II dose of MK-0646 in combination with standard etoposide and cisplatin chemotherapy
Outcome Description:
Evaluate safety, tolerability in combination with standard chemotherapy.
Outcome Time Frame:
Each dose level
Safety Issue:
No
Principal Investigator
Peter Ellis, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Margaret and Charles Juravinski Cancer Centre
Authority:
Canada: Health Canada
Study ID:
I190
NCT ID:
NCT00869752
Start Date:
January 2009
Completion Date:
July 2012
Related Keywords:
- Lung Cancer
- 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
- Lung Neoplasms
- Small Cell Lung Carcinoma
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