Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Participants With Non-Small Cell Lung Cancer Who Have Not Been Previously Treated With Chemotherapy

• ClinicalTrials.gov Identifier: NCT00533429
• Recruitment Status: Completed
• First Posted: September 21, 2007
• Results First Posted: May 13, 2021
• Last Update Posted: May 13, 2021
• Sponsor: Eli Lilly and Company
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of this study is to determine if Pemetrexed plus Carboplatin plus Bevacizumab plus Enzastaurin, followed by maintenance Bevacizumab plus Enzastaurin can extend survival time without disease progression in the first-line treatment of participants with advanced stage non-small cell lung cancer.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: enzastaurin; Drug: pemetrexed; Drug: carboplatin; Drug: bevacizumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Protocol H6Q-MC-S034(a) Randomized, Double-Blind, Phase 2 Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Chemonaive Patients With Stage IIIB or IV Non-Small Cell Lung Cancer
• Study Start Date: October 2007
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin	Drug: enzastaurin; 1125 milligram (mg) loading dose then 500 mg, oral, daily until disease progression; Other Name: LY317615; Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles; Other Names: LY231514; Alimta; Drug: carboplatin; Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles; Drug: bevacizumab; 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles
Placebo Comparator: B; Pemetrexed + Carboplatin + Bevacizumab + Placebo	Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles; Other Names: LY231514; Alimta; Drug: carboplatin; Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles; Drug: bevacizumab; 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles; Drug: Placebo; oral, daily

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Randomization to measured PD or death from any cause up to 12.2 months ]
   PFS was defined as the time from date of randomization to the first observation of progressive disease (PD) or death due to any cause. For participants not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of the last objective progression-free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to objective disease progression or death, PFS was censored at the date of the last objective progression-free assessment prior to the initiation of post-discontinuation anticancer therapy.

Secondary Outcome Measures :

1. Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) [ Time Frame: Randomization to measured progressive disease or death from any cause up to 12.2 months ]

   Tumor response rate was defined as number of participants with overall best response of CR or PR over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case, no new lesions may have appeared.

   Percentage of participants was calculated as: (number of participants with CR or PR/ number of participants qualified for tumor response analysis) × 100.

2. Overall Survival (OS) [ Time Frame: Randomization to date of death up to 14.3 months ]
   OS was defined as the time from the date of randomization to the date of death from any cause. For participants who were not known to have died as of the data cutoff, OS was censored at the last contact date.
3. Time to Progressive Disease (TTPD) [ Time Frame: Randomization to measured PD or death from any cause up to 12.2 months ]
   TTPD was defined as the time from the date of randomization until the first date of objectively determined progressive disease (PD). For participants who died without objective PD (including death from study disease), TTPD was censored at the date of the last objective progression-free disease assessment. For participants not known to have died as of the data cutoff and did not have PD, TTPD was censored at the date of the last objective progression-free disease assessment.
4. Duration of Response (DoR) [ Time Frame: Time of response to disease progression or death from any cause up to 12.2 months ]
   The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target lesions and PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as reference the baseline sum of LDs. For participants who died without progressive disease or who were alive, DoR was censored at the last contact of progression free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to PD, DoR was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. Due to early study closure, DoR was not analyzed.
5. Pharmacology Toxicity and Adverse Events (AEs) [ Time Frame: Randomization up to 14.3 months and 30-day follow-up ]
   Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs. Participants who died due to progressive disease (PD) or an AE while on treatment and or died during the 30 day post-treatment follow-up are included. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• participants or their legal representative must have signed an informed consent document for clinical research
• have laboratory confirmed diagnosis of advanced, nonsquamous cell non-small cell lung cancer (NSCLC) (Stage IIIB or IV disease) which is not curable
• have not received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy for advanced NSCLC, prior radiation therapy is allowed to less than 25% of the bone marrow
• have measurable disease
• have adequate organ function and estimated life expectancy of 12 weeks

Exclusion Criteria:

• have known central nervous system (CNS) disease; major surgery within 28 days; minor surgery within 7 days; serious concomitant systemic disorder; serious cardiac condition; have a serious, nonhealing wound, ulcer, or bone fracture
• have received treatment within the last 30 days with any drug that has not received regulatory approval for any indication at the time of study entry
• have previously received treatment with enzastaurin, pemetrexed, or bevacizumab
• are pregnant or breast-feeding
• are unable to swallow tablets

Contacts and Locations

Locations

United States, Arkansas

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Bentonville, Arkansas, United States, 72712

United States, Illinois

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Chicago, Illinois, United States, 60611

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Galesburg, Illinois, United States, 61401

United States, Indiana

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Bloomington, Indiana, United States, 47403

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Evansville, Indiana, United States, 47714

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Fort Wayne, Indiana, United States, 46815

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Indianapolis, Indiana, United States, 46202

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Lafayette, Indiana, United States, 47904

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Muncie, Indiana, United States, 47303

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

South Bend, Indiana, United States, 46601

United States, Michigan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Jackson, Michigan, United States, 49201

United States, Nebraska

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Omaha, Nebraska, United States, 68114

Sponsors and Collaborators

Eli Lilly and Company

Genentech, Inc.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00533429
• Other Study ID Numbers: 11398; H6Q-MC-S034 ( Other Identifier: Eli Lilly and Company )
• First Posted: September 21, 2007
• Results First Posted: May 13, 2021
• Last Update Posted: May 13, 2021
• Last Verified: April 2021

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Bevacizumab; Carboplatin; Pemetrexed; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors