A Study LY2228820 for Recurrent Ovarian Cancer

Fallopian Tube Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01663857
• Other study ID #: 12517
• Secondary ID: I1D-MC-JIAE
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2012
• Est. completion date: May 11, 2018

Study information

• Verified date: August 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: May 11, 2018
• Est. primary completion date: May 25, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Primary Peritoneal Cancer

Intervention

Drug:
• LY2228820
Administered Orally
• Carboplatin
Administered IV
• Placebo
Administered Orally
• Gemcitabine
Administered IV

Locations

Country	Name	City	State
Australia	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.	Adelaide
Australia	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	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	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
Belgium	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.	Leuven
Germany	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.	Berlin
Germany	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	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	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	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	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
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Austin	Texas
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Bedford	Texas
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Fort Worth	Texas
United States	SMO Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	St Josephs Hospital and Medical Center	Phoenix	Arizona
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	H Lee Moffitt Cancer Center	Tampa	Florida
United States	Texas Oncology - The Woodlands	The Woodlands	Texas
United States	US Oncology	The Woodlands	Texas
United States	Arizona Oncology Associates, P.C.	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists PC	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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)