SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01663857

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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

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

NCT01663857 Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer
MeSH: Ovarian Neoplasms Carcinoma, Ovarian Epithelial Fallopian Tube Neoplasms
HPO: Fallopian tube carcinoma Ovarian neoplasm

4 Interventions

Name: LY2228820

Description: Administered Orally

Type: Drug

Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) Phase 1b (Cohort 2) LY2228820 300 mg Phase 2 (Arm A) LY2228820 200 mg

Name: Carboplatin

Description: Administered IV

Type: Drug

Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) Phase 1b (Cohort 2) LY2228820 300 mg Phase 2 (Arm A) LY2228820 200 mg Phase 2 (Arm B) Placebo

Name: Placebo

Description: Administered Orally

Type: Drug

Phase 2 (Arm B) Placebo

Name: Gemcitabine

Description: Administered IV

Type: Drug

Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) Phase 1b (Cohort 2) LY2228820 300 mg Phase 2 (Arm A) LY2228820 200 mg Phase 2 (Arm B) Placebo


Primary Outcomes

Description: 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).

Measure: Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])

Time: Cycle 1 (21 Days)

Description: 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.

Measure: Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin

Time: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

Secondary Outcomes

Description: 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.

Measure: Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)

Time: Baseline to Disease Progression (up to 3 years)

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

Measure: Phase 2: Overall Survival

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

Description: PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.

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

Time: 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

Description: 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.

Measure: Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score

Time: Baseline, Study Completion (up to 3 years)

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 Q12H

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. --- Q12H ---



HPO Nodes


HPO:
Fallopian tube carcinoma
Ovarian neoplasm
Genes 63
RAD51 RAD51C PMS1 RAD51D CDKN2A KRAS SOX9 TGFBR2 FLI1 MRE11 MSH6 PMS2 MLH3 BRIP1 DMRT3 WWOX BRCA1 LMNA BRCA2 INHBA PIK3CA VAMP7 NR0B1 WRN CHEK2 GATA4 WT1 PTCH2 BARD1 MLH1 WNT10A NBN AKT1 C11ORF95 PRKN SRY EWSR1 RELA NR5A1 MSH2 MSH3 FGFR2 KEAP1 IDH1 IDH2 CTNNB1 PTCH1 PTEN SUFU CDH1 EPCAM DICER1 STAG3 RNF43 PALLD PALB2 OPCML TP53 MAP3K1 ZFPM2 SMAD4 FAN1 RAD50