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

Primary Purpose

Lung Cancer

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

anti-IGF-1R recombinant monoclonal antibody MK-0646

cisplatin

etoposide

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Juravinski Cancer Centre at Hamilton Health Sciences
Ottawa Health Research Institute - General Division
Univ. Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

MK-0646, a monoclonial antibody in combination with etoposide and cisplatin.

Outcomes

Primary Outcome Measures

Recommended phase II dose of MK-0646 in combination with standard etoposide and cisplatin chemotherapy

Evaluate safety, tolerability in combination with standard chemotherapy.

Toxicity and tolerability according to NCI CTCAE v3.0

Look at toxicity and tolerability of MK0646 in combination with standard therapy.

Preliminary efficacy

Look for evidence of response

Objective response rate

Determine objective response rate including complete response rate, progression free survival and overall survival.

Predictive and prognostic impact of biomarkers

Blood samples will be collected and analyzed for occurrence of human-anti-humanized antibody response to MK0646 as well as IGF-1R analysis.

Secondary Outcome Measures

Full Information

NCT ID

NCT00869752

First Posted

March 25, 2009

Last Updated

August 3, 2023

Sponsor

NCIC Clinical Trials Group

Collaborators

Merck Frosst Canada Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT00869752

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

December 16, 2009 (Actual)

Primary Completion Date

March 15, 2012 (Actual)

Study Completion Date

July 4, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NCIC Clinical Trials Group

Collaborators

Merck Frosst Canada Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

MK-0646, a monoclonial antibody in combination with etoposide and cisplatin.

Intervention Type

Biological

Intervention Name(s)

anti-IGF-1R recombinant monoclonal antibody MK-0646

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

cisplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

etoposide

Intervention Description

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

Primary Outcome Measure Information:

Title

Recommended phase II dose of MK-0646 in combination with standard etoposide and cisplatin chemotherapy

Description

Evaluate safety, tolerability in combination with standard chemotherapy.

Time Frame

Each dose level

Title

Toxicity and tolerability according to NCI CTCAE v3.0

Description

Look at toxicity and tolerability of MK0646 in combination with standard therapy.

Time Frame

Phase 1, each dose level and Phase II

Title

Preliminary efficacy

Description

Look for evidence of response

Time Frame

Phase 1 dose levels, evey other cycle

Title

Objective response rate

Description

Determine objective response rate including complete response rate, progression free survival and overall survival.

Time Frame

Phase II portion, every other cycle

Title

Predictive and prognostic impact of biomarkers

Description

Blood samples will be collected and analyzed for occurrence of human-anti-humanized antibody response to MK0646 as well as IGF-1R analysis.

Time Frame

Each cycle

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peter Ellis, MD

Organizational Affiliation

Margaret and Charles Juravinski Cancer Centre

Official's Role

Study Chair

Facility Information:

Facility Name

Juravinski Cancer Centre at Hamilton Health Sciences

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8V 5C2

Country

Canada

Facility Name

Ottawa Health Research Institute - General Division

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1H 8L6

Country

Canada

Facility Name

Univ. Health Network-Princess Margaret Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

Citation

J Clin Oncol 30, 2012 (suppl; abstr 7093)

Results Reference

result

PubMed Identifier

24518092

Citation

Ellis PM, Shepherd FA, Laurie SA, Goss GD, Olivo M, Powers J, Seymour L, Bradbury PA. NCIC CTG IND.190 phase I trial of dalotuzumab (MK-0646) in combination with cisplatin and etoposide in extensive-stage small-cell lung cancer. J Thorac Oncol. 2014 Mar;9(3):410-3. doi: 10.1097/JTO.0000000000000058.

Results Reference

result

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

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