Clinical trial NCT01663857: A Study LY2228820 for Recurrent Ovarian Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-08-13
Enrollment: 118
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])
timeFrame: Cycle 1 (21 Days)
measure: Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin
timeFrame: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)
Secondary outcomes:
measure: Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)
timeFrame: Baseline to Disease Progression (up to 3 years)
measure: Phase 2: Overall Survival
timeFrame: Baseline to Date of Death from any cause (up to 5 years)
measure: Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820
timeFrame: 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
measure: Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score
timeFrame: Baseline, Study Completion (up to 3 years)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St Josephs Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, P.C.
state: Arizona
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Franklin Square Hospital Center
state: Maryland
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: SMO Sarah Cannon Research Inst.
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology - The Woodlands
state: Texas
city: The Woodlands
country: United States
facility: US Oncology
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Vancouver
country: United States
facility: Northwest Cancer Specialists PC
state: Washington
city: Adelaide
country: Australia
facility: 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.
city: Greenslopes
country: Australia
facility: 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.
city: Nedlands
country: Australia
facility: 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.
city: Parkville
country: Australia
facility: 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.
city: Leuven
country: Belgium
facility: 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.
city: Berlin
country: Germany
facility: 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.
city: Essen
country: Germany
facility: 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.
city: Essen
country: Germany
facility: 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.
city: Greifswald
country: Germany
facility: 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.
city: Mainz
country: Germany
facility: 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.
city: München
country: Germany
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time *UTC/GMT-5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: 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.