A Study Evaluating Dalotuzumab (MK-0646) in Combination With Erlotinib for Participants With Non-Small Cell Lung Cancer (MK-0646-007)

NCT ID: NCT00654420

Last Updated: 2018-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-19
• Study Completion Date: 2012-02-13

Brief Summary

This is a Phase I/IIa study to evaluate safety and efficacy of dalotuzumab (MK-0646) in combination with erlotinib in participants with recurrent Non-Small Cell Lung Cancer (NSCLC). The Phase I part of this study will determine the highest tolerated dose of dalotuzumab to be given in combination with erlotinib. The primary hypothesis for the Phase I part of the study is that administration of erlotinib in combination with dalotuzumab in participants with recurrent NSCLC is generally well-tolerated as evidenced by accumulated safety data from this trial. The Phase II part of this study will investigate how well dalotuzumab works in conjunction with erlotinib at treating recurrent NSCLC. The primary hypothesis for the Phase II part of this study is that administration of erlotinib in combination with dalotuzumab in participants with recurrent NSCLC results in improvement in Progression Free Survival (PFS) compared to participants treated with erlotinib alone. PFS is defined as the time from randomization until either the emergence of radiographic evidence of disease progression (as documented by an independent core laboratory) or death due to any cause, whichever occurs first.

Detailed Description

Dalotuzumab is a humanized monoclonal antibody (mAb) that targets the Insulin-like Growth Factor Receptor (IGF-1R). Dalotuzumab may act through:

• Inhibition of IGF-1-mediated cell signaling to cause reductions in tumor growth and spread
• Antibody dependent cell-mediated cytotoxicity

In preclinical studies, dalotuzumab improved the activity of an anti-Epidermal Growth Factor Receptor (EGFR) mAb and the activity of Erlotinib, a small molecule inhibitor of EGFR

Trial Duration of Treatment: Participants will continue on the study for as long as their disease is not progressing and they do not have unmanageable side effects from the treatment.

Conditions

Carcinoma, Non-small-cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ph I: Dalotuzumab 5 mg/kg + Erlotinib

During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug.

Group Type: EXPERIMENTAL

Dalotuzumab

Intervention Type: DRUG

Dalotuzumab 20 mg/mL in sterile solution. Intravenous (IV) infusion over 60 minutes at 5 mg/kg, administered weekly at dosage according to treatment group.

Ph I: Dalotuzumab 10 mg/kg + Erlotinib

During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug.

Group Type: EXPERIMENTAL

Dalotuzumab

Intervention Type: DRUG

Dalotuzumab 20 mg/mL in sterile solution. Intravenous (IV) infusion over 60 minutes at 5 mg/kg, administered weekly at dosage according to treatment group.

Ph II: Dalotuzumab 10 mg/kg + Erlotinib

During the Phase II part of the study, participants are randomized to receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.

Group Type: EXPERIMENTAL

Dalotuzumab

Intervention Type: DRUG

Dalotuzumab 20 mg/mL in sterile solution. Intravenous (IV) infusion over 60 minutes at 5 mg/kg, administered weekly at dosage according to treatment group.

Ph II: Erlotinib

During the Phase II part of the study, participants are randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.

Group Type: ACTIVE_COMPARATOR

Erlotinib

Intervention Type: DRUG

Open-label erlotinib administrated orally (tablets) by mouth (PO) at 150 mg daily.

Interventions

Dalotuzumab

Dalotuzumab 20 mg/mL in sterile solution. Intravenous (IV) infusion over 60 minutes at 5 mg/kg, administered weekly at dosage according to treatment group.

Intervention Type: DRUG

Erlotinib

Open-label erlotinib administrated orally (tablets) by mouth (PO) at 150 mg daily.

Intervention Type: DRUG

Other Intervention Names

MK-0646; Tarceva; Erlotinib hydrochloride

Eligibility Criteria

Inclusion Criteria

• Participant has locally advanced or metastatic stage IIIB/IV NSCLC that has relapsed after hemotherapy/chemoratiotherapy
• Participant has had at least one chemotherapy regimen for recurrent or metastatic disease
• Participant is 18 years of age or older
• Participant has a performance status of 0-2 on Eastern Cooperative Group (ECOG) scale
• Women of childbearing potential have a negative pregnancy test

Exclusion Criteria

• Participant has had chemotherapy within 2 weeks or biological therapy (e.g. bevacizumab) within 4 weeks
• Participant has not recovered from adverse events from previous therapy within 4 weeks
• Participant has received EGFR-Tyrosine Kinase Inhibitor (TKI) inhibitor/anti-EGFR mAb therapy
• Participant has received IGF1R-TKI inhibitor/anti-IGF1R mAB therapy
• Participant has had more than 2 systemic chemotherapies for metastatic disease
• Participant has not completed radiotherapy with complete resolution of toxicities at least 2 weeks before starting in the study
• Participant is taking part in another clinical study
• Participant has a primary central nervous system tumor
• Participant abuses drugs or alcohol
• Participant is pregnant or breastfeeding
• Participant is Human Immunodeficiency Virus (HIV) positive
• Participant has a history of hepatitis B or C
• Participant is using growth hormone or growth hormone inhibitors

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Moran T, Felip E, Keedy V, Borghaei H, Shepherd FA, Insa A, Brown H, Fitzgerald T, Sathyanarayanan S, Reilly JF, Mauro D, Hsu K, Yan L, Johnson DH. Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: a phase I/II randomized trial. Exp Hematol Oncol. 2014 Nov 7;3(1):26. doi: 10.1186/2162-3619-3-26. eCollection 2014.

Reference Type: RESULT

PMID: 25414803 (View on PubMed)

Study Documents

Document Type: CSR Synopsis Link

View Document

Other Identifiers

2007_605

Identifier Type: OTHER

Identifier Source: secondary_id

2007-005941-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0646-007

Identifier Type: -

Identifier Source: org_study_id