First Line Chemotherapy Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT00308750
• Recruitment Status: Completed
• First Posted: March 30, 2006
• Results First Posted: May 13, 2021
• Last Update Posted: May 13, 2021
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purposes of this study are to determine:

The safety of enzastaurin plus pemetrexed with carboplatin, pemetrexed with carboplatin, or docetaxel with carboplatin and any side effects that might be associated with the combination of these drugs.

Whether the combination of enzastaurin plus pemetrexed and carboplatin or pemetrexed and carboplatin can help participants with non-small cell lung cancer (NSCLC) live longer, compared with the combination of docetaxel and carboplatin.

Whether the combination of enzastaurin plus pemetrexed and carboplatin or pemetrexed and carboplatin can make your tumor smaller or disappear, and for how long, compared with the combination of docetaxel and carboplatin.

The effects of enzastaurin plus pemetrexed with carboplatin, pemetrexed with carboplatin or docetaxel with carboplatin have on your disease related symptoms.

The relation of smoking history and hormone replacement therapy (for women only) may have to your lung cancer treatment results.

The effects of certain genes and proteins in samples of your blood and tumor tissue in order to learn more about NSCLC and how enzastaurin works in the body.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: enzastaurin; Drug: pemetrexed; Drug: docetaxel; Drug: carboplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label Phase II Study of Pemetrexed (Alimta) Plus Carboplatin With or Without Enzastaurin Hydrochloride, or Docetaxel Plus Carboplatin as First Line Treatment in Patients With Advanced Stage Non-small Cell Lung Cancer (NSCLC)
• Study Start Date: March 2006
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Enzastaurin/Pemetrexed/Carboplatin	Drug: enzastaurin; 1125-1200 milligrams (mg) loading dose then 500 mg, oral, daily, until disease progression; Other Name: LY317615; Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease; Other Names: LY231514; Alimta; Drug: carboplatin; Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease
Experimental: Pemetrexed/Carboplatin	Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease; Other Names: LY231514; Alimta; Drug: carboplatin; Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease
Active Comparator: Docetaxel/Carboplatin	Drug: docetaxel; 75 mg/m^2, IV, q 21 days, six 21 day cycles or progressive disease; Drug: carboplatin; Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease

Outcome Measures

Primary Outcome Measures :

1. Time to Disease Progression [ Time Frame: Baseline to measured PD up to 22.3 months ]
   Time to disease progression was defined as the time from randomization to the first date of documented disease progression or death if the participant dies due to disease progression. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions. For participants who have not had documented disease progression, time to disease progression was censored at the date of death or date of last visit. For participants who received other anti-tumor therapy prior to disease progression, time to disease progression was censored at the first available date of other anti-tumor therapy.

Secondary Outcome Measures :

1. Tumor Biomarkers Associated With Clinical Outcomes [ Time Frame: Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up ]
   As specified in the protocol, tumor biomarker samples were collected from participants on the pemetrexed arms only but were not intended to be analyzed at the individual study level.
2. Assessment of Smoking History (All Participants) and Hormone Replacement Therapy (Female Participants Only) Associated With Clinical Outcomes [ Time Frame: Baseline ]
   Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level.
3. Number of Participants With Adverse Events (AEs) or Deaths [ Time Frame: Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up ]
   Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, or deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events section of this report.
4. Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale [ Time Frame: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each] ]
   The FACT-L version 4 scale is used to assess health-related quality of life (HRQoL) in participants with lung cancer. The FACT-L has 5 subscales: Physical Well-Being (PWB), Social and Family Well-Being (SFWB) and Functional Well-Being (FWB) subscales which include 7 items each, Emotional Well-Being (EWB) subscale which includes 6 items, and a Lung-Cancer Specific (LCS) subscale which include 7 items. Total FACT-L is the sum of all 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 equal to "worst quality of life" to 136 equal to "best quality of life". The Least Square (LS) mean was calculated using an analysis of covariance (ANCOVA) model adjusted for change scores and baseline scores.
5. Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale [ Time Frame: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each] ]
   The FACT-Taxane version 4 scale is used to assess HRQoL in participants receiving taxane chemotherapy. The FACT-taxane has 5 subscales: PWB, SFWB, and FWB subscales which include 7 items each, EWB subscale which includes 6 items, and a taxane subscale which include 16 items and has two domains (neurotoxicity and taxane). Total FACT-Taxane is the sum of all the 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 "worst quality of life" to 172 "best quality of life". The LS mean was calculated using an ANCOVA model adjusted for change scores and baseline scores.
6. Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause up to 35 months ]
   OS was the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact.
7. Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] [ Time Frame: Baseline to measured PD up to 22.3 months ]
   Response was defined using RECIST, version 1.0 criteria. Participants with a best response of CR or PR were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
8. Duration of CR or PR (Duration of Response) [ Time Frame: Date of first response to the date of progression or death due to any cause up to 22.3 months ]
   The duration of a CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death due to any cause. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
9. Time-to-Treatment Failure (TTF) [ Time Frame: Baseline to stopping treatment up to 14.1 months ]
   TTF was defined as the time from randomization to the first observation of PD, death due to any cause, or early discontinuation of treatment. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions. TTF was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.

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:

• You must have been diagnosed with NSCLC.
• You must be able to visit the doctor's office weekly during the active treatment period and as needed during the study follow-up period.
• You must be willing and able to swallow capsules.
• Your entry labs and medical tests must meet study requirements.
• You must be willing to have blood samples drawn and tissue samples obtained for gene and protein testing.

Exclusion Criteria:

• You have received radiation within 2 weeks of study enrollment.
• You have previously received any anti-cancer drug therapy for NSCLC.
• You have an active infection or other serious condition.
• You take aspirin or aspirin-like medication regularly and are not able to stop taking them for a few days during each cycle of chemotherapy.
• You have recently lost a significant amount of weight.

Contacts and Locations

Locations

United States, North Carolina

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.

Burlington, North Carolina, United States, 27215

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.

Chapel Hill, North Carolina, United States, 27599

United States, South Carolina

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.

Columbia, South Carolina, United States, 29210

United States, Texas

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.

Houston, Texas, United States, 77060

Sponsors and Collaborators

Eli Lilly and Company

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Socinski MA, Raju RN, Stinchcombe T, Kocs DM, Couch LS, Barrera D, Rousey SR, Choksi JK, Jotte R, Patt DA, Periman PO, Schlossberg HR, Weissman CH, Wang Y, Asmar L, Pritchard S, Bromund J, Peng G, Treat J, Obasaju CK. Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer. J Thorac Oncol. 2010 Dec;5(12):1963-9. doi: 10.1097/JTO.0b013e3181fd42eb.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00308750
• Other Study ID Numbers: 10651; H6Q-US-S004 ( Other Identifier: Eli Lilly and Company )
• First Posted: March 30, 2006
• 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; Carboplatin; Docetaxel; Pemetrexed; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors