SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01526928

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)

Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.

NCT01526928 Locally Advanced or Metastatic Non Small Cell Lung Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

Name: Rociletinib

Description: Phase 1: Rociletinib will be administered in escalating dosages in a period of 21-day cycles Phase 2: Rociletinib will be administered daily

Type: Drug

Rociletinib


Primary Outcomes

Measure: Objective Response Rate (ORR) and duration of response per RECIST Version 1.1 by investigator assessment

Time: Cycle 1 Day 1 to End of Treatment

Secondary Outcomes

Measure: Objective Response Rate (ORR), duration of response and progression-free survival (PFS) per RECIST Version 1.1 as determined by IRR

Time: Cycle 1 Day 1 to End of Treatment / End of Follow-up

Measure: Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities

Time: Cycle 1 Day 1 to End of Treatment

Measure: Overall survival (OR), disease control rate (DCR), and progression-free survival (PFS) per RECIST Version 1.1 as determined by investigator assessment

Time: Cycle 1 Day 1 to End of Treatment / End of Follow-up

Measure: Plasma PK parameters for rociletinib at Cycle 1 Day 1 and Cycle 1 Day 15 (subset of patients); rociletinib metabolite profiling in Day 15 plasma samples (subset of patients); rociletinib based on sparse sampling of all patients

Time: Cycle 1 Day 1 to End of Treatment

Measure: Change from baseline in patient reported outcomes using the Dermatology Life Quality Index, the EORT QLQ - LC13, and the EORT QLQ-C30

Time: Cycle 1 Day 1 to End of Treatment

Measure: Change from baseline in QT/QTc interval

Time: Cycle 1 Day 1 to End of Treatment

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T790M

The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation. --- T790M ---

Adequate hematological and biological function 7. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation Phase 2 Cohorts must also meet the following inclusion criteria: - Disease progression confirmed by radiologic assessment while on treatment with EGFR- TKI Or - Disease progression confirmed by radiologic assessment while on treatment with the first single agent EGFR TKI and - Documented evidence of T790M mutation in EGFR following disease progression on the first single agent EGFR TKI. - Measureable disease according to RECIST Version 1.1 Exclusion Criteria - Any of the following criteria will exclude patients from study participation: 1. Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene 2. Active second malignancy 3. Known pre-existing interstitial lung disease 4. Patients with Leptomeningeal carcinomatosis are excluded. --- T790M ---

Other CNS metastases are only permitted if treated, asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of study treatment). 5. Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib 6. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting rociletinib 7. Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR 8. Certain cardiac abnormalities or history 9. Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib 10. --- T790M ---

However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. --- T790M ---

Nonclinical data demonstrate that rociletinib inhibits T790M. --- T790M ---

It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs. --- T790M ---

It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs. --- T790M --- --- T790M ---

This study will include 2 parts: Phase 1 (completed enrolment): Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22 Phase 2 (currently enrolling): Evaluation of activity and safety in patients with the T790M EGFR mutation who have: Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy --- 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
Non-small cell lung carcinoma
Genes 2
TP53 BAP1