Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment
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|ClinicalTrials.gov Identifier: NCT04263090|
Recruitment Status : Recruiting
First Posted : February 10, 2020
Last Update Posted : July 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Adenocarcinoma Stage IV||Drug: Rigosertib Drug: Nivolumab||Phase 1 Phase 2|
This is an open-label, dose-escalating Phase I study followed by a Phase 2a dose-expansion phase to study the combination of Rigosertib and Nivolumab in metastatic Kirsten rat sarcoma positive (KRAS+) lung adenocarcinoma patients who have progressed on standard first line treatment. Study patients will have satisfied the inclusion/exclusion criteria enumerated in this protocol. The Phase I dose escalation plan will start with an accelerated titration design (ATD) using single patient cohorts until grade 2 toxicity is experienced. At that point, the ATD will be terminated and the dose escalation will enter a standard 3+3 design based on dose-limiting toxicities (DLT). The MTD (Phase 1 primary endpoint) is defined as the highest dose for which at most 1 patient out of 6 experiences a DLT.
Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg in the morning (qAM), 280mg in the evening (qPM); dose D3: 560mg twice daily; taken by mouth for 21 consecutive days of the 28 day cycle), based on previous dose escalation studies in other malignancies, while Nivolumab dose will be fixed at the standard dose (240mg every 2 weeks, given intravenously).
Once the MTD is determined, an additional planned 12 patients will be enrolled in the expansion phase to further study toxicity and to determine preliminary efficacy endpoints including ORR (phase 2a primary endpoint), PFS, and OS (secondary endpoints) of the combination.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
Dose-escalating Phase I study followed by a Phase 2a dose-expansion phase.
Rigosertib escalation will occur with three dose levels: Dose D1: 280mg twice daily, Dose D2: 560mg qAM, 280mg qPM, Dose D3: 560mg twice daily. Nivolumab will be dosed at the standard fixed dose of 240mg.
|Masking:||None (Open Label)|
|Official Title:||A Phase1/2a Study of Rigosertib Plus Nivolumab in Stage IV Lung Adenocarcinoma Patients With KRAS Mutation Who Progressed on First-Line Treatment|
|Actual Study Start Date :||June 29, 2020|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||January 2022|
Experimental: Rigosertib + Nivolumab
Rigosertib + Nivolumab in metastatic KRAS+ lung adenocarcinoma patients
Rigosertib will be dosed twice a day for 21 consecutive days, followed by 7 days off treatment (each cycle duration: 28 days). Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg qAM, 280mg qPM; dose D3: 560mg twice daily).
Nivolumab will be dosed once ever 2 weeks (twice per 28-day cycle; standard fixed dose of 240mg).
- Maximal Tolerated Dose (MTD) [ Time Frame: DLTs will be evaluated at the end of Cycle 1 (each cycle is 28 days) ]MTD is defined as the highest dose for which at most 1 patient out of 6 experiences a dose-limiting toxicity (DLT)
- Overall Response Rate (ORR) [ Time Frame: 2 years ]ORR is defined as achieving an objective response of either complete response or partial response
- Progression Free Survival (PFS) [ Time Frame: 2 years ]Phase 2: PFS is defined as the duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier.
- Overall Survival (OS) at MTD [ Time Frame: 2 years ]Phase 2: OS at MTD is defined as the time from the first dose of study treatment to the date of death (whatever the cause).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04263090
|Contact: Rajwanth Veluswamy, MD, MSCR||(212) email@example.com|
|Contact: Joseph LaValle, BAfirstname.lastname@example.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Rajwanth Veluswamy, MD, MSCR 212-824-8580 email@example.com|
|Contact: Joseph LaValle, BA 2128247376 firstname.lastname@example.org|
|Principal Investigator: Rajwanth Veluswamy, MD, MSCR|
|Principal Investigator:||Rajwanth Veluswamy, MD, MSCR||Icahn School of Medicine at Mount Sinai|