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Report for Clinical Trial NCT04256941

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

INTERACT- Integrated Evaluation of Resistance and Actionability Using Circulating Tumor DNA in HR Positive Metastatic Breast Cancers

This phase II trial studies how well letrozole, anastrozole, or fulvestrant work when given together with ribociclib, palbociclib, and/or abemaciclib in treating patients with hormone receptor (HR) positive breast cancer that has spread to other places in the body (metastatic) and has an ERS1 activating mutation. Letrozole, anastrozole, ribociclib, palbociclib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known if giving letrozole, anastrozole, or fulvestrant with ribociclib, palbociclib, and/or abemaciclib will work better in treating patients with breast cancer.

NCT04256941 Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8
MeSH:Breast Ne Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast

6 Interventions

Name: Abemaciclib

Description: Given PO
Type: Drug
Group Labels: 2

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant) Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Name: Anastrozole

Description: Given PO
Type: Drug
Group Labels: 1

Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Name: Fulvestrant

Description: Given IM
Type: Drug
Group Labels: 1

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant)

Name: Letrozole

Description: Given PO
Type: Drug
Group Labels: 1

Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Name: Palbociclib

Description: Given PO
Type: Drug
Group Labels: 2

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant) Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Name: Ribociclib

Description: Given PO
Type: Drug
Group Labels: 2

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant) Arm II (ribociclib, palbociclib, abemaciclib, letrozole)


Primary Outcomes

Description: Survival curves for PFS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

Measure: Progression-free survival (PFS)

Time: Up to 30 days

Secondary Outcomes

Description: Graphical analysis, such as scatter plots with Lowess smoothers, will be used to assess the correlative structure of outcomes and compare MAF between fulvestrant and aromatase inhibitor-treated groups. The Pearson correlation, or its non-parametric analogue, the Spearman correlation, will be used to estimate the linear correlation among variables.

Measure: Circulating tumor deoxyribonucleic acid (ctDNA) ESR1 mutant allele fraction (MAF) and kinetics

Time: Up to 30 days

Description: Will be assessed by the secondary resistance of endocrine therapy.

Measure: Prevalence of Emergence of Estrogen Receptor 1 (ESR1) mutations

Time: Up to 30 days

Description: Will correlate ctDNA with CA 15-3 tumor marker changes.

Measure: Changes in cancer antigens (CA) 15-3 tumor marker

Time: Up to 30 days

Description: Survival curves for OS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

Measure: Overall survival (OS)

Time: Up to 30 days

Description: Will be assessed on next line of therapy after progression.

Measure: Time to next treatment

Time: Up to 30 days

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 3 SNPs

SNPs


1 D538G

D538G, Y537S/N, S463P) identified on ctDNA. --- D538G ---


2 S463P

D538G, Y537S/N, S463P) identified on ctDNA. --- D538G --- --- Y537S --- --- S463P ---


3 Y537S

D538G, Y537S/N, S463P) identified on ctDNA. --- D538G --- --- Y537S ---



HPO Nodes


HPO: