A Study in Ovarian, Non-Small Cell Lung, Prostate, Colorectal, Gastroesophageal Cancers, and Squamous Cell Carcinoma of the Head and Neck

• ClinicalTrials.gov Identifier: NCT01059643
• Recruitment Status: Completed
• First Posted: February 1, 2010
• Results First Posted: December 4, 2017
• Last Update Posted: September 18, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of the study is to estimate the rate of response for patients with ovarian, non-small cell lung, prostate, colorectal, gastroesophageal, and head and neck cancers who are administered LY2523355.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Non Small Cell Lung Cancer; Prostate Cancer; Colorectal Cancer; Gastric Cancer; Esophageal Cancer; Cancer of Head and Neck	Drug: LY2523355; Drug: pegfilgrastim	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 103 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Indication Identification Study of LY2523355 in Patients With Ovarian, Non-Small Cell Lung, Prostate, Colorectal, Gastroesophageal Cancers, and Squamous Cell Carcinoma of the Head and Neck
• Study Start Date: April 2011
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm

Intervention/treatment

Experimental: LY2523355

Drug: LY2523355; Dose determined by participant body surface area: 5 milligrams/square meter(mg/m²) or 6 mg/m², administered intravenously as a 1-hour infusion on Days 1, 2 and 3 of a 21 day cycle; for up to 2 cycles (4 cycles for prostate cancer patients). Additional cycles administered based on patient response assessment.; Drug: pegfilgrastim; 6 milligrams (mg), administered subcutaneously approximately 24 hours after third dose of LY2523355 on Day 4 of each 21-day cycle, for up to 2 cycles of LY2523355 administration (4 cycles for prostate cancer patients). Additional cycles of LY2523355 administered based on patient response assessment.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline until progressive disease up to 36 weeks post-baseline ]
   The percentage of participants who achieved a best response of either CR or PR, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Percentage is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

Secondary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Date of enrollment to progressive disease or death due to any cause up to 36 weeks post-enrollment ]
   PFS defined as the time from date of first dose to the first observation of disease progression or death due to any cause. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 millimeter (mm) increase over nadir. For participants who were not known to have died or to have progressed as of the data inclusion cutoff date, PFS were censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy.
2. Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [ Time Frame: Baseline until progressive disease up to 36 weeks post-baseline ]
   Response using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria.
3. Tumor Marker Values as Relevant to Specific Tumor Types at Baseline [ Time Frame: Baseline ]
   The number of participants with colorectal cancer (CRC), gastroesophageal cancer (GE), non-small cell lung cancer (NSCLC), ovarian cancer, prostate cancer or squamous cell carcinoma of head and neck (SCCHN) who had marker/molecular diagnostics performed prior to study entry to determine the mutation status of cancer genes: APC, BRAF, BRCA1, BRCA2, HRAS and KRAS and the presence of Human Papillovirus (HPV) and Epstein Barr viruses (EBV). Mutation/virus status was defined as: positive (mutation/virus present), negative (mutation/virus not present), unknown (mutation/virus status unknown), or not done (mutation/virus status was not done).
4. Change in Tumor Size at Smallest Size (Best Response) [ Time Frame: Baseline until cycle with maximum change from baseline up to 36 weeks ]
   The percent change in tumor size at its smallest size. The sum of diameters of target lesions was determined at each tumor assessment. The percent change is the smallest post-baseline sum divided by the baseline (pre-treatment) sum, multiplied by 100.
5. Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 [ Time Frame: Day 3 of Cycle 1 (21-day cycle) ]
   Plasma Cmax following daily doses of LY2523355 on Days 1, 2, and 3 of Cycle 1 (21-day cycle).
6. Pharmacokinetics, Intracycle Accumulation Ratio (Ra) of LY2523355 [ Time Frame: Day 1 and Day 3 of Cycle 1 (21-day cycle) ]
   Intracycle Ra of LY2523355 is the ratio of LY2523355 maximum plasma concentration (Cmax) on Day 3 of Cycle 1 to the Cmax of LY2523355 on Day 1 of Cycle 1 following daily doses of LY2523355 on Days 1, 2 and 3 of Cycle 1 (21-day cycle) at each dose level.

Other Outcome Measures:

1. Number of Participants Who Died Due to Unknown Causes During the 30-Day Post-Study Treatment Follow-Up [ Time Frame: End of study treatment up to 30-days post-study treatment discontinuation ]

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:

• Diagnosis of ovarian, non-small cell lung, prostate, colorectal, gastroesophageal cancer (adenocarcinoma of the esophageal cancer, stomach, or gastroesophageal junction), or squamous cell cancer of the head and neck
• Have measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines (except prostate cancer participants)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Are willing to follow study procedures for the duration of the study
• Are willing to use an approved contraceptive method during treatment and for 3 months after discontinuation of study treatment

Exclusion Criteria:

• Have a serious preexisting medical condition that would preclude participation in the study
• Are pregnant or lactating
• Have received treatment within 28 days of first dose of LY2523355 with a drug that has not received regulatory approval for any indication
• Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases
• Have a second active primary malignancy or a history of a second malignancy requiring cytotoxic therapy
• Have QTc interval greater than 470 millisecond (msec) or intraventricular conduction delay (IVCD) with QRS greater than 120 msec on screening electrocardiogram (ECG)
• Have active symptomatic fungal, bacterial, and/or known viral infection including active human immunodeficiency virus (HIV) or viral (A, B, C) hepatitis
• Participants with pneumonia, evidence of obstructive pneumonitis, other respiratory infections, or infection from other sources are to be excluded

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.

Jonesboro, Arkansas, United States, 72401

United States, Florida

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.

Jacksonville, Florida, United States, 32256

United States, Georgia

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.

Macon, Georgia, United States, 31201

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Marietta, Georgia, United States, 30060

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.

Valdosta, Georgia, United States, 31602

United States, Idaho

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.

Post Falls, Idaho, United States, 83854

United States, Kansas

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.

Westwood, Kansas, United States, 66205

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.

Wichita, Kansas, United States, 67214

United States, Louisiana

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.

Baton Rouge, Louisiana, United States, 70809

United States, Maryland

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Bethesda, Maryland, United States, 20817

United States, Montana

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.

Billings, Montana, United States, 59102

United States, Ohio

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.

Columbus, Ohio, United States, 43219

United States, Oklahoma

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.

Oklahoma City, Oklahoma, United States, 73120

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.

Charleston, South Carolina, United States, 29425

United States, Tennessee

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.

Germantown, Tennessee, United States, 38138

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.

Memphis, Tennessee, United States, 38120

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.

Corpus Christi, Texas, United States, 78404

United States, West Virginia

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.

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

Eli Lilly and Company

Investigators

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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01059643
• Other Study ID Numbers: 12848; I1Y-MC-JFBF ( Other Identifier: Eli Lilly and Company )
• First Posted: February 1, 2010
• Results First Posted: December 4, 2017
• Last Update Posted: September 18, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

Additional relevant MeSH terms:

Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell