SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01877811

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

An Open-Label, Phase 1/1b, Single-Agent Study of RXDX-105 in Patients With Advanced Solid Tumors

This is a first-in-human, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Phase 1b is a dose expansion in approximately 90 patients with advanced solid tumors with specific histologies and/or molecular alterations of interest. Patients in Phase 1b will be treated at the RP2D determined in Phase 1.

NCT01877811 Solid Tumors

1 Interventions

Name: RXDX-105

Description: During Phase 1/1b, subjects will receive daily oral doses of RXDX-105 in 28-day cycles (except for Day 2 of Cycle 1). To determine the recommended Phase 2 dose (RP2D), doses will be administered in an escalated fashion starting at 20 mg/day. During Phase 1b, subjects will be administered the RP2D in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment.

Type: Drug

RXDX-105


Primary Outcomes

Description: From signing of the informed consent up to approximately 12 months

Measure: Phase 1: Dose Limiting Toxicities

Time: Approximately 12 months

Description: From signing of the informed consent up to approximately 12 months

Measure: Phase 1: Occurrence of Adverse Events

Time: Approximately 12 months

Description: To further assess the safety profile and tolerability of RXDX-105 at the RP2D

Measure: Phase 1b: Occurrence of Adverse Events

Time: Approximately 12 months

Secondary Outcomes

Measure: Phase 1: Maximum observed plasma drug concentration (Cmax)

Time: Day 1 to Day 16

Measure: Phase 1: Time of maximum observed plasma drug concentration (tmax)

Time: Day 1 to Day 16

Measure: Phase 1: Area under the plasma drug concentration versus time curve from time 0 to infinity (AUC0-∞)

Time: Day 1 to Day 16

Measure: Phase 1: Area under the plasma drug concentration versus time curve from time 0 to the last measureable drug concentration (AUC0-t)

Time: Day 1 to Day 16

Measure: Phase 1: Area under the plasma drug concentration versus time curve from time 0 to 24 hours after study drug administration (AUC0-24)

Time: Day 1 to Day 16

Measure: Phase 1: Terminal elimination rate constant (λz)

Time: Day 1 to Day 16

Measure: Phase 1: Terminal elimination half-life (t1/2)

Time: Day 1 to Day 16

Measure: Phase 1: Apparent clearance of study drug from plasma (CL/F)

Time: Day 1 to Day 16

Description: Objective response rate is defined as the proportion of patients with advanced solid tumors achieving best overall response of complete response (CR), or partial response (PR), as assessed using RECIST v1.1

Measure: Phase 1b: Objective Response Rate

Time: Approximately 12 months

Description: The duration of objective response is defined as the time interval from the date of first documented response (CR or PR) to disease progression or death, whichever occurs first

Measure: Phase 1b: Duration of Objective Response

Time: Approximately 12 months

Description: Clinical benefit rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) for 6 months

Measure: Phase 1b: Clinical Benefit Rate

Time: Approximately 12 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E ---

Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E ---

Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E --- --- V600E ---

Known hypersensitivity to any of the components of RXDX-105 Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E ---

Known hypersensitivity to any of the components of RXDX-105 Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E ---

Known hypersensitivity to any of the components of RXDX-105 Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E --- --- V600E ---



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