Safety Study of KPT-330 (Selinexor) in Patients With Advanced or Metastatic Solid Tumor Cancer
Condition: Solid Tumor
MeSH terms: Neoplasms
Intervention: Selinexor; Acetaminophen
Intervention description: 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.; 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)
Intervention MeSH terms: Acetaminophen
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 192.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Selinexor; KPT-330; Squamous Cell Carcinoma; Glioblastoma multiforme; Adenocarcinoma; Melanoma; Colorectal cancer; Gynecological cancer; Castrate-resistant Prostate Cancer; Other solid tumors

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no
             standard therapy is available. For Schedule 6 only: patients with colorectal cancer
             with liver metastasis.

             Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy
             with 1 of the following diagnoses, which has been confirmed histologically or
             cytologically:

               -  Up to 12 patients with metastatic colorectal cancer with a history of progression
                  or recurrence following prior fluoropyrimidine, irinotecan and platinum
                  containing regimens as well as bevacizumab. In addition, patients with Kras wild
                  type tumor must have received at least one EGFR blocker.

               -  Up to 6 patients with histological or cytological documentation of advanced
                  ovarian, fallopian tube, or primary peritoneal carcinoma with a history of
                  progression or recurrence following at least one prior platinum and one taxane
                  based chemotherapy

               -  Up to 12 patients with incurable Squamous cell cancers as follows:

                    1. A minimum of 4 Squamous Non-Small Cell Lung Cancer (Sq-NSCLC)

                    2. A minimum of 4 Squamous Cell Carcinomas of the Head and Neck (Sq-HNC)

                    3. Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell
                       Carcinomas should have a documented history of progression or recurrence
                       following at least one prior platinum based chemotherapy or
                       chemotherapy/radiation containing regimen

               -  Up to 6 patients with castration-resistant prostate cancer (CRPC) that was
                  pathologically confirmed as adenocarcinoma of the prostate and with evidence of
                  metastatic disease on bone scan or other imaging. Patient must have progressive
                  disease after at least one hormonal treatment and one cytotoxic therapy e.g. with
                  docetaxel, mitoxantrone.

               -  Up to 12 patients with unresectable metastatic melanoma whose disease progressed
                  on at least 1 prior systemic anticancer regimen (chemotherapy, biological or
                  immunotherapy, or targeted therapy). Enrollment to this cohort may have been
                  stopped before reaching 12 patients once the dose-escalation portion of the study
                  was completed.

               -  Approximately 6 patients with advanced or metastatic solid tumors were to be
                  enrolled on Schedule 8 at a starting dose of 35 mg/m^2 to assess general
                  tolerability and activity of selinexor.

          2. Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from,
             further conventional therapy and have evidence of progressive disease on study entry.

        Both Dose Escalation and Expansion Phases: There is no upper limit on the number of prior
        treatments provided that all inclusion criteria are met and exclusion criteria are not met.
        Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not
        considered anticancer regimes.

        Exclusion Criteria:

          1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks
             prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1
             day 1;

          2. Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS
             malignancy are excluded. Asymptomatic small lesions are not considered active. Treated
             lesions may be considered inactive if they are stable for at least 3 months.