SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01562028

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

An Open-label Phase II Trial of Erlotinib and Bevacizumab in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations

Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. The investigators hypothesize that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways. The investigators propose a model of treatment whereby patients with EGFR mutations (single or with T790M) can attain a benefit with longer overall PFS when treated with erlotinib plus bevacizumab. When the patients are grouped by BRCA1 mRNA levels and T790M the hypothesis is that the combination of erlotinib plus bevacizumab can improve the PFS in all subgroups.

NCT01562028 Lung Cancer
MeSH: Lung Neoplasms
HPO: Neoplasm of the lung

2 Interventions

Name: Erlotinib

Description: Patients will be treated with erlotinib, 150 mg p.o., daily

Type: Drug

Erlotinib plus bevacizumab

Name: Bevacizumab

Description: Patients will be treated with bevacizumab 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days)

Type: Drug

Erlotinib plus bevacizumab


Primary Outcomes

Description: Time from the date of enrolment until documented progression or death, whichever occurs first.

Measure: Progression free survival

Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient

Secondary Outcomes

Description: Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death).

Measure: Time to treatment failure

Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient

Description: Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment.

Measure: Objective response

Time: termination of trial treatment

Description: Adverse events graded according to NCI CTCAE V4.

Measure: Adverse events

Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient

Description: Achievement of objective response or stable disease for at least 6 weeks.

Measure: Disease control

Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient

Description: Interval from the date of first documentation of objective response by RECIST to the date of first documented progression or relapse.

Measure: Duration of response

Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient

Description: Time from the date of enrolment until death from any cause.

Measure: Overall survival (OS)

Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient

Purpose: Treatment

Single Group Assignment


There are 2 SNPs

SNPs


1 L858R

BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC) Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. --- L858R ---

- Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R) Exclusion Criteria: - Patients with increased risk of bleeding - Patients with clinically significant cardiovascular diseases - Patients with a history of thrombosis or thromboembolism in the 6 months prior to treatment - Patients with gastrointestinal problems - Patients with neurologic problems - Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma. --- L858R ---


2 T790M

The investigators hypothesize that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways. --- T790M ---

The investigators propose a model of treatment whereby patients with EGFR mutations (single or with T790M) can attain a benefit with longer overall PFS when treated with erlotinib plus bevacizumab. --- T790M ---

When the patients are grouped by BRCA1 mRNA levels and T790M the hypothesis is that the combination of erlotinib plus bevacizumab can improve the PFS in all subgroups. --- T790M ---

To determine long-term outcome of patients with advanced non-squamous NSCLC harbouring EGFR mutations with or without T790M mutation at diagnosis and treated with the combination of erlotinib and bevacizumab. --- T790M ---

Primary endpoint: progression-free survival 2. To evaluate the efficacy and tolerability of the combination 3. To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival 4. To monitor EGFR mutations (including T790M) in serum and plasma longitudinally 5. To evaluate molecular biomarkers related to EGFR TKI and bevacizumab Design: This is a multinational, multi-center phase II trial of erlotinib plus bevacizumab in patients with advanced non-squamous NSCLC harbouring EGFR mutations confirmed by central re-assessment. --- T790M ---

Primary endpoint: progression-free survival 2. To evaluate the efficacy and tolerability of the combination 3. To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival 4. To monitor EGFR mutations (including T790M) in serum and plasma longitudinally 5. To evaluate molecular biomarkers related to EGFR TKI and bevacizumab Design: This is a multinational, multi-center phase II trial of erlotinib plus bevacizumab in patients with advanced non-squamous NSCLC harbouring EGFR mutations confirmed by central re-assessment. --- T790M --- --- T790M ---

Patients will be stratified into two subgroups, with and without EGFR T790M mutation. --- T790M ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN