A study for women with ovarian cancer that has returned at least 6 months after platinum-based chemotherapy.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
118
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).
Time frame: 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.
Time frame: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)
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.
Time frame: 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.
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Administered IV
St Josephs Hospital and Medical Center
Phoenix, Arizona, United States
Arizona Oncology Associates, P.C.
Tucson, Arizona, United States
Sarasota Memorial Hospital
Sarasota, Florida, United States
H Lee Moffitt Cancer Center
Tampa, Florida, United States
Franklin Square Hospital Center
Baltimore, Maryland, United States
Barnes Jewish Hospital
St Louis, Missouri, 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
SMO Sarah Cannon Research Inst.
Nashville, Tennessee, United States
...and 20 more locations
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Study Completion (up to 3 years)