Clinical trial NCT00654420: A Study Evaluating Dalotuzumab (MK-0646) in Combination With Erlotinib for Participants With Non-Small Cell Lung Cancer (MK-0646-007)
Official title: An Open Label, Randomized Phase I/IIa Trial Evaluating MK-0646 in Combination With Erlotinib (TARCEVA™) for Patients With Recurrent Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-small-cell Lung
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-04-08
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Phase I: Number of Participants Experiencing at Least One Dose-Limiting Toxicity (DLT) Adverse Event (AE) During the First Four Weeks of Dalotuzumab Plus Erlotinib Treatment
timeFrame: Up to 4 weeks after initiation of treatment
measure: Phase II: Median Progression Free Survival (PFS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment
timeFrame: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)
Secondary outcomes:
measure: Phase II: Median Overall Survival (OS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment
timeFrame: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)
measure: Phase II: Percentage of Participants With Complete Response (CR) or Partial Response (PR) After Dalotuzumab Plus Erlotinib Treatment (Objective Response Rate [ORR])
timeFrame: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.