A Study LY2228820 for Recurrent Ovarian Cancer
- Conditions
- Epithelial Ovarian CancerPrimary Peritoneal CancerFallopian Tube Cancer
- Interventions
- Registration Number
- NCT01663857
- Lead Sponsor
- Eli Lilly and Company
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 118
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) LY2228820 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. Phase 1b (Cohort 2) LY2228820 300 mg LY2228820 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. Phase 2 (Arm A) LY2228820 200 mg LY2228820 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. Phase 2 (Arm B) Placebo 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. Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) Carboplatin 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. Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) Gemcitabine 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. Phase 1b (Cohort 2) LY2228820 300 mg Gemcitabine 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. Phase 1b (Cohort 2) LY2228820 300 mg Carboplatin 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. Phase 2 (Arm A) LY2228820 200 mg Carboplatin 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. Phase 2 (Arm A) LY2228820 200 mg Gemcitabine 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. Phase 2 (Arm B) Placebo Carboplatin 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. Phase 2 (Arm B) Placebo Gemcitabine 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.
- Primary Outcome Measures
Name Time Method Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD]) Cycle 1 (21 Days) 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).
Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin Randomization to Date of Disease Progression or Death from any cause (up to 3 years) 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.
- Secondary Outcome Measures
Name Time Method Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate) Baseline to Disease Progression (up to 3 years) 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.
Phase 2: Overall Survival Baseline to Date of Death from any cause (up to 5 years) Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.
Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820 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 PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.
Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score Baseline, Study Completion (up to 3 years) 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.
Trial Locations
- Locations (17)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Arizona Oncology Associates, P.C.
🇺🇸Tucson, Arizona, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Franklin Square Hospital Center
🇺🇸Baltimore, Maryland, United States
H Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
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
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Texas Oncology - The Woodlands
🇺🇸The Woodlands, Texas, United States
Northwest Cancer Specialists PC
🇺🇸Vancouver, Washington, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Fort Worth, Texas, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
St Josephs Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
SMO Sarah Cannon Research Inst.
🇺🇸Nashville, Tennessee, United States
Cancer Care Centers of South Texas
🇺🇸San Antonio, Texas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States