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A Study LY2228820 for Recurrent Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01663857
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : May 29, 2019
Last Update Posted : September 11, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Drug: LY2228820 Drug: Carboplatin Drug: Placebo Drug: Gemcitabine Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : July 2012
Actual Primary Completion Date : May 25, 2017
Actual Study Completion Date : May 11, 2018


Arm Intervention/treatment
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
Administered Orally

Drug: Carboplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Names:
  • Gemzar
  • LY188011

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
Administered Orally

Drug: Carboplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Names:
  • Gemzar
  • LY188011

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
Administered Orally

Drug: Carboplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Names:
  • Gemzar
  • LY188011

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
Administered IV

Drug: Placebo
Administered Orally

Drug: Gemcitabine
Administered IV
Other Names:
  • Gemzar
  • LY188011




Primary Outcome Measures :
  1. Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD]) [ Time Frame: 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).

  2. Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin [ Time Frame: 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 :
  1. Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate) [ Time Frame: 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.

  2. Phase 2: Overall Survival [ Time Frame: 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.

  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 [ 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 ]
    PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.

  4. Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01663857


Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time *UTC/GMT-5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] March 16, 2017
Statistical Analysis Plan  [PDF] September 21, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01663857    
Other Study ID Numbers: 12517
I1D-MC-JIAE ( Other Identifier: Eli Lilly and Company )
First Posted: August 13, 2012    Key Record Dates
Results First Posted: May 29, 2019
Last Update Posted: September 11, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Gemcitabine
Carboplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs