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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Carcinoma, Non-small-cell Lung

Treatments: Drug: Erlotinib; Drug: Dalotuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00654420

2007-005941-39 (EudraCT Number)

0646-007

2007_605 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 95 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

95 participants in 4 patient groups

Ph I: Dalotuzumab 5 mg/kg + Erlotinib

Experimental group

Description:

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.

Treatment:

Drug: Dalotuzumab

Ph I: Dalotuzumab 10 mg/kg + Erlotinib

Experimental group

Description:

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.

Treatment:

Drug: Dalotuzumab

Ph II: Dalotuzumab 10 mg/kg + Erlotinib

Experimental group

Description:

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.

Treatment:

Drug: Dalotuzumab

Ph II: Erlotinib

Active Comparator group

Description:

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.

Treatment:

Drug: Erlotinib