A Study LY2228820 for Recurrent Ovarian Cancer

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• Ovarian Neoplasms 2,695
• Carcinoma, Ovarian Epithelial 1,617
• Fallopian Tube Neoplasms 720

Ovarian Neoplasms

2,695 studies on the registry are indexed under Ovarian Neoplasms; 727 are open to participants now.

This study's enrollment of 118 is above the median of 60 across 2,030 interventional studies indexed under Ovarian Neoplasms.

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Study arms

• 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: LY2228820 · Drug: Carboplatin · Drug: Gemcitabine

• 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: LY2228820 · Drug: Carboplatin · Drug: Gemcitabine

• 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: LY2228820 · Drug: Carboplatin · Drug: Gemcitabine

• 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 · Drug: Placebo · Drug: Gemcitabine

Interventions

• DrugLY2228820

  Administered Orally

• DrugCarboplatin

  Administered IV

• DrugPlacebo

  Administered Orally

• DrugGemcitabine

  Administered IV

  Also known as: Gemzar, LY188011

Primary outcomes

1. 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)

2. 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)

Secondary outcomes

1. 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)

2. Phase 2: Overall Survival

   Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.

   Time frame: Baseline to Date of Death from any cause (up to 5 years)

3. 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

4. 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)

Baseline characteristics

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. PubMed 31791552 ↗

Study documents

• Study protocol · Mar 16, 2017
• Statistical analysis plan · Sep 21, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Csr