Clinical trial NCT01607905
Conditions: Solid Tumor
Keywords: Selinexor KPT-330 Squamous Cell Carcinoma Glioblastoma multiforme Adenocarcinoma Melanoma Colorectal cancer Gynecological cancer Castrate-resistant Prostate Cancer Other solid tumors
Sponsor: Karyopharm Therapeutics Inc
Start date: 2012-06-18; Completion date: 2016-03-15
Enrollment: 192 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies.

Detailed description:
This is a phase 1a and phase 1b, open-label, dose-escalation study to evaluate the safety and tolerability of selinexor and determine the RP2D in patients with solid tumor malignancies.

Arms: arm 1: Participants with colorectal cancer and liver metastasis received oral selinexor as single agent in 8 schedules, Schedule1: ≤12milligrams per meter square(mg/m\^2) 3 times weekly(TIW) during Weeks 1 and 3, twice weekly(BIW) during Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule2: \>12mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule3: ≥30mg/m\^2 BIW(Days 1 and 3) up to 8 doses/cycle(28 days/cycle); Schedule4: ≥20mg/m\^2 BIW(Days 1 and 2) up to 8 doses/cycle(28 days/cycle); Schedule5: ≥35mg/m\^2 BIW(Days 1 and 4) up to 8 doses(28 days/cycle); Schedule6: ≥20mg/m\^2 BIW(Days 1 and 4) after 500 mg(Week 1) to 1000 mg(Week 2 onwards) acetaminophen(given 1 hour prior to each selinexor dose) up to 8 doses/cycle (28 days/cycle); Schedule7: ≥50mg/m\^2 once weekly(QW) up to 4 doses/cycle(28 days per cycle); Schedule8: ≥45mg/m\^2 BIW(Days 1 and 3) up to 4 doses/cycle(21 days/cycle), until disease progression, death, or unacceptable toxicity. arm 2: Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. arm 3: Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. arm 4: Participants with castrate-resistant prostate cancer (CRPC) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. arm 5: Participants with glioblastoma multiforme (GBM) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. arm 6: Participants with Melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. arm 7: Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.
Interventions: intervention 1: Selinexor intervention 2: Acetaminophen
Intervention descriptions: intervention 1: Participants in this study will receive selinexor orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m\^2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in 4-week (28 days for schedule 1 to 7) and 3-week (21 days for schedule 8) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted. intervention 2: Oral 500 mg (in Cycle 1, Week 1) to 1000 mg (in Cycle 1, Week 2 and onwards) of acetaminophen will be administered 1 hour prior to each selinexor dose up to 8 doses per cycle (28 days per cycle)

Protocol documents: