A Study LY2228820 for Recurrent Ovarian Cancer

A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38 MAPK Inhibitor, Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin for Women With Platinum-Sensitive Ovarian Cancer

A study for women with ovarian cancer that has returned at least 6 months after platinum-based chemotherapy.

Study Overview

• Status: Completed
• Conditions: Fallopian Tube Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Gemcitabine; Drug: Placebo; Drug: LY2228820

Detailed Description

Phase 1b is unblinded and will have a small number of participants that will take LY2228820 plus gemcitabine and carboplatin to test the safety of the combination and determine a recommended dose for the Phase 2 portion.

Phase 2 will be blinded and all study participants will receive carboplatin and gemcitabine. Participants of one group will receive LY2228820, and the other group will receive placebo.

If the participant achieves at least stable disease, there is a maintenance phase following the first 6 cycles. The participant will take either LY2228820 or placebo. The participant will continue therapy until disease progression or other discontinuation criteria are fulfilled.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • 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.
  • Greenslopes, Australia, 4120
    • 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.
  • Nedlands, Australia, 6009
    • 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.
  • Parkville, Australia, 3053
    • 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.
• Belgium
  • Leuven, Belgium, 3000
    • 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.
• Germany
  • Berlin, Germany, 10117
    • 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.
  • Essen, Germany, 45122
    • 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.
  • Essen, Germany, 45136
    • 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.
  • Greifswald, Germany, 17489
    • 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.
  • Mainz, Germany, 55131
    • 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.
  • München, Germany, 81675
    • 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.
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St Josephs Hospital and Medical Center
    • Tucson, Arizona, United States, 85710
      • Arizona Oncology Associates, P.C.
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SMO Sarah Cannon Research Inst.
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology - The Woodlands
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Have been diagnosed with ovarian, fallopian tube, or primary peritoneal cancer
• Have been treated one time with a platinum-based chemotherapy and your disease has come back at least six months after you completed treatment
• Are able to swallow tablets
• Have given written informed consent prior to any study procedures
• Have adequate blood counts, hepatic and renal function
• Have performance status equal to or less than 2 on Eastern Cooperative Oncology Group (ECOG) scale
• Have negative pregnancy test, and if participant is of child bearing potential must use birth control while on study and for three months after stopping study drug

Exclusion Criteria:

• Have been previously treated with Gemcitabine for ovarian, fallopian tube or primary peritoneal cancer
• Are currently enrolled or discontinued less than 14 days from another clinical trial
• Have a history of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• Have taken certain medications or had grapefruit juice within 7 days of initial dose of study drug, as levels of the study drug may be affected.
• Must not be pregnant or breastfeeding.
• Have malignancy or metastasis of the central nervous system
• Have borderline malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b (Cohort 1) LY2228820 200 milligrams (mg); Cohort 1: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 milligrams per square meter (mg/m^2) administered intravenously (IV) over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.. Cohort 1: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.	Drug: Carboplatin; Administered IV; Drug: Gemcitabine; Administered IV; Other Names: Gemzar; LY188011; Drug: LY2228820; Administered Orally
Experimental: Phase 1b (Cohort 2) LY2228820 300 mg; Cohort 2: Cycles 1-6 (21 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Cohort 2: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.	Drug: Carboplatin; Administered IV; Drug: Gemcitabine; Administered IV; Other Names: Gemzar; LY188011; Drug: LY2228820; Administered Orally
Experimental: Phase 2 (Arm A) LY2228820 200 mg; Arm A: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Arm A: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.	Drug: Carboplatin; Administered IV; Drug: Gemcitabine; Administered IV; Other Names: Gemzar; LY188011; Drug: LY2228820; Administered Orally
Placebo Comparator: Phase 2 (Arm B) Placebo; Arm B: Cycles 1-6 (21 day cycles)- Placebo administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Arm B: Cycle 7+ (28 day cycles)- Placebo administered orally on days 1-14 to maintain blind.	Drug: Carboplatin; Administered IV; Drug: Gemcitabine; Administered IV; Other Names: Gemzar; LY188011; Drug: Placebo; Administered Orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])	Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).	Cycle 1 (21 Days)
Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin	PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)	Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.	Baseline to Disease Progression (up to 3 years)
Phase 2: Overall Survival	Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.	Baseline to Date of Death from any cause (up to 5 years)
Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820	PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.	Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD
Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score	The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.	Baseline, Study Completion (up to 3 years)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Vergote I, Heitz F, Buderath P, Powell M, Sehouli J, Lee CM, Hamilton A, Fiorica J, Moore KN, Teneriello M, Golden L, Zhang W, Pitou C, Bell R, Campbell R, Farrington DL, Bell-McGuinn K, Wenham RM. A randomized, double-blind, placebo-controlled phase 1b/2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. Gynecol Oncol. 2020 Jan;156(1):23-31. doi: 10.1016/j.ygyno.2019.11.006. Epub 2019 Nov 29.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): May 25, 2017
• Study Completion (Actual): May 11, 2018

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: August 9, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Actual): September 11, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin
• Other Study ID Numbers: 12517; I1D-MC-JIAE (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR