Ignite Creation Date:
2025-12-25 @ 4:25 AM
Ignite Modification Date:
2025-12-26 @ 3:28 AM
Study NCT ID:
NCT03875820
Status:
UNKNOWN
Last Update Posted:
2023-07-10
First Post:
2018-11-15
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Phase I Trial of Defactinib and VS-6766.
Sponsor:
Institute of Cancer Research, United Kingdom
Organization:
Study Overview
Official Title:
FRAME: A Phase I Trial of the Combination of Defactinib (VS-6063) (FAK Inhibitor) and VS-6766 (RO5126766) (CH5126776) (a Dual RAF/MEK Inhibitor) in Patients With Advanced Solid Tumours
Status:
UNKNOWN
Status Verified Date:
2023-07
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FRAME
Brief Summary:
This is a multi-centre, investigator-initiated, dose escalation, Phase I trial of the combination of the FAK inhibitor, Defactinib (VS-6063), and the dual RAF/MEK inhibitor, VS-6766 (RO5126766) in patients with advanced solid tumours. VS-6766 (RO5126766) is the same compound as CH5126766.
There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). This will be followed by a dose expansion phase to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.
There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). This will be followed by a dose expansion phase to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.
Detailed Description:
This is a multi-centre, investigator-initiated, dose escalation, Phase I trial of the combination of the FAK inhibitor, Defactinib, and the dual RAF/MEK inhibitor, VS-6766 in patients with advanced solid tumours.
There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients were enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Up to 24 patients with solid tumours were treated in the dose escalation phase of this study.
The dose escalation phase is now closed to recruitment.
This will be followed by a dose expansion phase of 86 patients to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.
The dose expansion phase is made up of 7 cohorts:
* 20 patients with KRAS mutant non-small-cell lung cancer (NSCLC);
* 7 patients with solid tumours (enriched for those with RAS mutations) willing to undergo biopsies at three time points throughout the study;
* 20 patients with low grade serous ovarian cancer (LGSOC);
* 10 patients with colorectal cancer (CRC);
* 10 patients with KRAS G12V mutant NSCLC;
* 10 patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis related) and
* 10 patients with pancreatic cancer.
The following cohorts are still open to recruitment:
* Patients with low grade serous ovarian cancer (LGSOC);
* Patients with KRAS G12V mutant NSCLC;
* Patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis-related) and
* Patients with pancreatic cancer.
Patients will take the two investigational medicinal products (IMPs) as follows:
VS-6766 will be administered orally twice a week on Monday/Thursday or Tuesday/Friday at least one hour prior or two hours after a meal. The starting dose of VS-6766 will be 3.2mg once a day, twice a week and can be escalated to a maximum of 4mg once a day, twice a week.
Defactinib will be administered orally twice a day immediately after a meal. The starting dose of Defactinib will be 200mg twice daily and can be escalated to a maximum of 400mg twice daily.
A cycle length is 4 weeks (28 days). Combination dosing (VS-6766 and Defactinib) will commence on Cycle 1 Day 1 for 3 weeks followed by one week without either drug in week 4 (i.e. 3 weeks on, 1 week off).
For patients consenting to optional biopsies, a run-in dose of VS-6766 will be administered on a single day anywhere between Days -7 to Day -3 in order to facilitate pharmacodynamic (PD) biomarker analysis. Therefore, for patients undergoing biopsies the first cycle will be 5 weeks long and subsequent cycles will consist of 4 weeks.
If this schedule is not tolerated, alternative schedules may be explored following discussion by the Safety Review Committee.
There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients were enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Up to 24 patients with solid tumours were treated in the dose escalation phase of this study.
The dose escalation phase is now closed to recruitment.
This will be followed by a dose expansion phase of 86 patients to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.
The dose expansion phase is made up of 7 cohorts:
* 20 patients with KRAS mutant non-small-cell lung cancer (NSCLC);
* 7 patients with solid tumours (enriched for those with RAS mutations) willing to undergo biopsies at three time points throughout the study;
* 20 patients with low grade serous ovarian cancer (LGSOC);
* 10 patients with colorectal cancer (CRC);
* 10 patients with KRAS G12V mutant NSCLC;
* 10 patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis related) and
* 10 patients with pancreatic cancer.
The following cohorts are still open to recruitment:
* Patients with low grade serous ovarian cancer (LGSOC);
* Patients with KRAS G12V mutant NSCLC;
* Patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis-related) and
* Patients with pancreatic cancer.
Patients will take the two investigational medicinal products (IMPs) as follows:
VS-6766 will be administered orally twice a week on Monday/Thursday or Tuesday/Friday at least one hour prior or two hours after a meal. The starting dose of VS-6766 will be 3.2mg once a day, twice a week and can be escalated to a maximum of 4mg once a day, twice a week.
Defactinib will be administered orally twice a day immediately after a meal. The starting dose of Defactinib will be 200mg twice daily and can be escalated to a maximum of 400mg twice daily.
A cycle length is 4 weeks (28 days). Combination dosing (VS-6766 and Defactinib) will commence on Cycle 1 Day 1 for 3 weeks followed by one week without either drug in week 4 (i.e. 3 weeks on, 1 week off).
For patients consenting to optional biopsies, a run-in dose of VS-6766 will be administered on a single day anywhere between Days -7 to Day -3 in order to facilitate pharmacodynamic (PD) biomarker analysis. Therefore, for patients undergoing biopsies the first cycle will be 5 weeks long and subsequent cycles will consist of 4 weeks.
If this schedule is not tolerated, alternative schedules may be explored following discussion by the Safety Review Committee.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2017-001035-39 | EUDRACT_NUMBER | None | View |