SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02037529

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Randomized Phase III Trial of Eribulin Compared to Standard Weekly Paclitaxel as First- or Second-Line Therapy for Locally Recurrent or Metastatic Breast Cancer

This randomized phase III trial studies how well eribulin mesylate or paclitaxel work as first- or second-line therapy in treating patients with stage IIIC-IV breast cancer that has come back. Drugs used in chemotherapy, such as eribulin mesylate and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

NCT02037529 Breast Adenocarcinoma HER2/Neu Negative Invasive Breast Carcinoma Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7
MeSH: Breast Neoplasms Adenocarcinoma
HPO: Breast carcinoma Neoplasm of the breast

4 Interventions

Name: Eribulin Mesylate

Description: Given IV

Type: Drug

Arm A (eribulin mesylate)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Arm A (eribulin mesylate) Arm B (paclitaxel)

Name: Paclitaxel

Description: Given IV

Type: Drug

Arm B (paclitaxel)

Name: Quality-of-Life Assessment

Description: Ancillary studies

Type: Other

Arm A (eribulin mesylate) Arm B (paclitaxel)


Primary Outcomes

Description: The patient-reported maximum score (post baseline) across Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items for each patient will be computed over the first 12 weeks and compared between arms using a two-sample independent samples t-test.

Measure: Patient-reported maximum score

Time: Up to 12 weeks after treatment initiation

Description: The Cox score test will be used to test the association between the cumulative dose level triggering toxicity and the genotype. The goal is to validate the EPHA5 rs7349683 single neucleotide polymorphism (SNP).

Measure: Validation of germline EPHA5 polymorphism (rs7349683)

Time: Up to 5 years

Secondary Outcomes

Description: The primary analysis will use the stratified log-rank tests, as described for overall survival. As a secondary analysis we will use a multivariable Cox proportional hazard model to estimate adjusted hazard ratios for eribulin mesylate over standard weekly paclitaxel, study stratification factors, and covariates for known prognostic factors, including disease free interval and visceral versus non-visceral metastases. Survival functions will be summarized using the Kaplan-Meier method according to treatment group.

Measure: Overall survival (OS)

Time: From randomization to death due to any cause, assessed up to 5 years

Description: The primary analysis will use the Cochran-Mantel-Haenszel chi-squared test with study stratification factors. Secondary analyses will use logistic regression to test differences in proportions while controlling for the covariates. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Objective tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Time: Up to 5 years

Description: Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Duration of response

Time: Up to 5 years

Description: Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Time to treatment failure

Time: Up to

Description: The primary analysis will use the Cochran-Mantel-Haenszel chi-squared test with study stratification factors. Secondary analyses will use logistic regression to test differences in proportions while controlling for the covariates. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Incidence of treatment related adverse events

Time: Up to 30 days after last dose assessed by CTCAE version 4.0

Description: Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Time to new metastasis

Time: Up to 5 years

Description: Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Progression free survival assessed by RECIST 1.1 criteria

Time: From randomization to progression or death due to any cause, whichever occurs first, assessed up to 5 years

Description: Additional analyses will include the previously described analysis conducted over the first 24 weeks; a comparison of the incidence of patient-reported maximum score >= 3 between arms through 12 and 24 weeks using chi-squared testing for each item; and a comparison of the time to patient-reported score >= 3 between arms using Kaplan-Meier and log-rank analyses. Further, these three endpoints will be compared between patient- and clinician-report overall and within arms using appropriate paired analyses.

Measure: Patient reported neurotoxicity

Time: Up to 24 weeks

Description: The PRO-CTCAE sensory neuropathy items will be further validated by computing Pearson correlations between each item and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20 )sensory scale score at baseline, 12 and 24 weeks.

Measure: Validation of PRO-CTCAE sensory neuropathy item

Time: At baseline, 12 and 24 weeks

Other Outcomes

Description: Will be summarized using the Kaplan-Meier method according to treatment group.

Measure: New metastasis free survival

Time: Up to 5 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 rs7349683

The patient-reported maximum score (post baseline) across Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items for each patient will be computed over the first 12 weeks and compared between arms using a two-sample independent samples t-test.. Validation of germline EPHA5 polymorphism (rs7349683).

The goal is to validate the EPHA5 rs7349683 single neucleotide polymorphism (SNP).. Overall survival (OS).

To validate rs7349683 in EPHA5 as a predictor of peripheral neuropathy from treatment with a microtubule targeting agent (i.e., eribulin or paclitaxel).



HPO Nodes


HPO:
Breast carcinoma
Genes 51
RAD51 RAD51C RAD51D CDKN2A KRAS MRE11 SLC22A18 STK11 MSH6 KLLN BRIP1 BRCA1 ATR BRCA2 PIK3CA PPM1D POLD1 NTHL1 POLE ESR1 WRN CHEK2 APC BARD1 MLH1 NBN COL14A1 AKT1 PRKN MSH2 FGFR2 IDH1 IDH2 CTNNB1 RB1CC1 PTEN MDM2 AAGAB CDH1 RNF43 PALLD PALB2 OPCML SEC23B TP53 SDHB SDHC SDHD SMAD4 TWIST1 RAD50
Neoplasm of the breast
Genes 73
RAD51 RAD51C RAD51D CDKN2A KRAS CDKN2B CDKN2D MRE11 SLC22A18 STK11 MSH6 RASGRP1 KLLN BRIP1 MGMT BRCA1 LMNA ATR ACD BRCA2 PIK3CA PPM1D POLD1 NTHL1 POLE ESR1 POT1 MC1R MITF WRN CHEK2 APC BARD1 MLH1 PRKAR1A CASP10 NBN PRKCD COL14A1 AKT1 C11ORF95 PRKN RELA MSH2 FGFR2 IDH1 GNAS IDH2 CTNNB1 RB1CC1 PTEN MDM2 FAS FASLG AAGAB CDH1 TERT RNF43 PALLD PALB2 OPCML TERF2IP PRLR SEC23B TP53 SDHB SDHC SDHD SMAD4 BAP1 CDK4 TWIST1 RAD50