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Report for Clinical Trial NCT01013506

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase II Trial of Endocrine Therapy in Combination With OSI-906 (an IGF-1R Inhibitor) With or Without Erlotinib (Tarceva, an EGFR Inhibitor) in Patients With Hormone-sensitive Metastatic Breast Cancer.

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole +/- goserelin (the latter for pre-menopausal women only) may fight breast cancer by lowering the amount of estrogen the body makes. OSI-906 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hormone therapy and OSI-906 are more effective when given with or without erlotinib hydrochloride in treating hormone-sensitive metastatic breast cancer. PURPOSE: This phase II trial is studying how well giving hormone therapy together with OSI-906 with or without erlotinib hydrochloride works in treating hormone-sensitive patients with metastatic breast cancer.

NCT01013506 Breast Cancer
MeSH: Breast Neoplasms
HPO: Breast carcinoma Neoplasm of the breast

4 Interventions

Name: IGF-1R inhibitor OSI-906

Description: Given orally

Type: Drug

Letrozole +/- goserelin, OSI-906, erlotinib (Arm II) Letrozole +/-goserelin, OSI-906 (Arm I )

Name: erlotinib hydrochloride

Description: Given orally

Type: Drug

Letrozole +/- goserelin, OSI-906, erlotinib (Arm II)

Name: goserelin

Description: Given subcutaneously

Type: Drug

Letrozole +/- goserelin, OSI-906, erlotinib (Arm II) Letrozole +/-goserelin, OSI-906 (Arm I )

Name: letrozole

Description: Given orally

Type: Drug

Letrozole +/- goserelin, OSI-906, erlotinib (Arm II) Letrozole +/-goserelin, OSI-906 (Arm I )


Primary Outcomes

Description: Duration from study enrollment to date of progressive disease (PD) as measured by Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: PD is > 20% increase in the sum of the longest diameter of target lesions or appearance of new lesions

Measure: Time to progression

Time: from study entry to date of progressive disease

Secondary Outcomes

Description: The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death

Measure: Safety profile of OSI-906 and letrozole +/ goserelin, with and without erlotinib

Time: at 4 weeks

Description: Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

Measure: Response

Time: every 12 weeks to progression

Description: Levels of the protein C-peptide and the hormone IGF-1 in the blood

Measure: Circulating C-peptide, IGF-1

Time: At baseline and on day 1 of each 28-day cycle

Description: The levels of these biomarkers will be measured in breast tumor tissue and compared and contrasted with patient's time to progression and molecular classification (luminal A vs. luminal B)

Measure: Correlation of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER expression with time to progression and molecular classification

Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery

Description: Breast tumor tissue will be examined for mutations in these genes.

Measure: Mutation analysis of PI3K (E542K, E545K, H1047R)

Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 3 SNPs

SNPs


1 E542K

Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K ---

- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer OUTLINE: This is a multicenter study. --- E542K ---


2 E545K

Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K --- --- E545K ---

- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer OUTLINE: This is a multicenter study. --- E542K --- --- E545K ---


3 H1047R

Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K --- --- E545K --- --- H1047R ---

- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer OUTLINE: This is a multicenter study. --- E542K --- --- E545K --- --- H1047R ---



HPO Nodes


HPO:
Breast carcinoma
Genes 95
TP53 PPM1D CTNNB1 TP53 COL14A1 AKT1 AKT1 OPCML MDM2 BRCA1 SLC22A18 POLE BRCA2 BRCA1 SDHC NTHL1 PTEN XRCC3 MSH6 IDH1 RAD51C RAD51C CASP8 RB1CC1 PIK3CA PALLD KRAS PIK3CA CHEK2 BRIP1 MRE11 NTHL1 ATM TP53 RAD51D STK11 PRKN ESR1 PIK3CA KLLN MSH2 SDHD KRAS SEC23B HMMR PTEN POLD1 PIK3CA IDH2 BRCA1 PALB2 BRIP1 TP53 RAD51 RNF43 BARD1 BARD1 AAGAB AKT1 SMAD4 RAD50 STK11 CHEK2 RAD54L NBN CDKN2A SEC23B CDH1 WRN NQO2 PALB2 ATR PALB2 TWIST1 SDHB MSH2 BRCA2 BRCA1 RAD51 CHEK2 MLH1 BRCA1 FGFR2 TP53 PHB BRCA2 CDH1 PTEN BRCA2 CHEK2 CDKN2A APC MLH1 AKT1 APC
Neoplasm of the breast
Genes 123
PPM1D CTNNB1 PTEN MGMT AKT1 BRCA1 SLC22A18 BRCA1 SDHC NTHL1 XRCC3 APC IDH1 LMNA RAD51C CDKN2B PIK3CA PALLD CHEK2 NTHL1 ATM RAD51D ESR1 GNAS APC PIK3CA RASGRP1 SDHD PRKCD KRAS BAP1 IDH2 PALB2 FAS RAD51 RNF43 PRLR AKT1 CHEK2 CDKN2A CDH1 CDK4 RELA BRCA2 BRCA1 TERF2IP CHEK2 MLH1 BRCA1 PRKAR1A POT1 BRCA2 CDH1 TERT APC MLH1 AKT1 TP53 CASP10 TP53 COL14A1 AKT1 OPCML MDM2 POLE BRCA2 PTEN MSH6 RAD51C CASP8 RB1CC1 KRAS ACD PIK3CA BRIP1 MRE11 TP53 STK11 PRKN KLLN MSH2 SEC23B HMMR PTEN POLD1 PIK3CA BRCA1 MITF FAS BRIP1 TP53 BARD1 BARD1 AAGAB SMAD4 RAD50 STK11 RAD54L NBN C11ORF95 SEC23B WRN PTEN NQO2 PTEN PALB2 ATR PALB2 CDKN2A TWIST1 SDHB MSH2 MC1R FASLG RAD51 FGFR2 TP53 PHB PTEN BRCA2 CHEK2 CDKN2A APC