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

NCT00654420 | Completed Phase 2 Results

• 3 other identifiers: 0646-0072007_6052007-005941-39
• Study Type: interventional
• Target: 95
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Carcinoma, Non-small-cell Lung

Outcome Measures

Primary Outcomes (2)

• 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

  A DLT was an AE related (definitely, probably, or possibly) to study therapy and occurring within first 4 weeks of therapy. Hematologic DLTs included Grade (Gr)4 neutropenia lasting for ≥7 days, Gr 3/Gr 4 neutropenia with fever \>38.5 °C and/or infection requiring antibiotic or anti-fungal treatment, and Gr 4 thrombocytopenia (25.0 x 10\^9/L). Non-hematologic DLT defined as any ≥Gr 3 nonhematologic toxicity, except Gr 3 reversible rash; Gr 3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia occurring in setting of inadequate compliance with supportive care; alopecia; anorexia; asthenia; inadequately-treated hypersensitivity reactions; Gr 3 elevated transaminases (≤1 week duration); or infusion reactions to dalotuzumab. Any drug-related AEs that led to dose modification of dalotuzumab/erlotinib or any unresolved drug-related toxicity that caused a ≥3 week delay of next scheduled dose of study drug, regardless of Common Terminology Criteria grade, were DLTs.

  Up to 4 weeks after initiation of treatment

• Phase II: Median Progression Free Survival (PFS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment

  PFS was defined as the time from randomization until either the emergence of radiographic evidence of disease progression or death due to any cause, whichever occurs first. Disease progression was classified as a radiographic assessment of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) using computed tomography (CT) or magnetic resonance imaging (MRI). As pre-specified by the protocol, final analysis of PFS was to take place after approximately 49 PFS events or deaths had occurred in the Phase II part of the trial. A non-parametric Kaplan-Meier method was used to estimate the median PFS time for each treatment group. Participants who discontinued from the study for reasons other than progression of disease were treated as right-censored observations at the time of the last response evaluation. Participants who withdrew from the study due to PD were considered to have a disease progression between the last visit and the time of withdrawal.

  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 (2)

• Phase II: Median Overall Survival (OS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment

  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)

• Phase II: Percentage of Participants With Complete Response (CR) or Partial Response (PR) After Dalotuzumab Plus Erlotinib Treatment (Objective Response Rate [ORR])

  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)

Study Arms (4)

Ph I: Dalotuzumab 5 mg/kg + Erlotinib

EXPERIMENTAL

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.

Drug: Dalotuzumab

Ph I: Dalotuzumab 10 mg/kg + Erlotinib

EXPERIMENTAL

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.

Drug: Dalotuzumab

Ph II: Dalotuzumab 10 mg/kg + Erlotinib

EXPERIMENTAL

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.

Drug: Dalotuzumab

Ph II: Erlotinib

ACTIVE COMPARATOR

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.

Drug: Erlotinib

Interventions

Dalotuzumab 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.

Also known as: MK-0646

Ph I: Dalotuzumab 10 mg/kg + Erlotinib; Ph I: Dalotuzumab 5 mg/kg + Erlotinib; Ph II: Dalotuzumab 10 mg/kg + Erlotinib

Erlotinib DRUG

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

Also known as: Tarceva, Erlotinib hydrochloride

Ph II: Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 25414803 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dalotuzumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2008
• First Posted: April 8, 2008
• Study Start: March 19, 2008
• Primary Completion: November 25, 2009
• Study Completion: February 13, 2012
• Last Updated: August 8, 2018
• Results First Posted: December 28, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share