Clinical Trials /

PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA)

NCT02702492

Description:

This study will evaluate the safety, tolerability, and efficacy of oral KPT-9274 for the treatment of patients with advanced solid malignancies or non-Hodgkin's lymphoma (NHL). Currently enrolling melanoma patients in combination with nivolumab, only.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA)
  • Official Title: A Phase 1 Open-Label Study of the Safety, Tolerability and Efficacy of KPT-9274, a Dual Inhibitor of PAK4 and NAMPT, in Patients With Advanced Solid Malignancies or Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: KCP-9274-901
  • NCT ID: NCT02702492

Conditions

  • NHL
  • Solid Tumors

Interventions

DrugSynonymsArms
KPT-9274KPT-9274
Niacin ERKPT-9274 & Niacin Extended Release (ER)
NivolumabOpdivo®KPT-9274 + Nivolumab

Purpose

This study will evaluate the safety, tolerability, and efficacy of oral KPT-9274 for the treatment of patients with advanced solid malignancies or non-Hodgkin's lymphoma (NHL).

Detailed Description

      This is a first-in-human, multi-center, open-label clinical study with separate Dose
      Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of
      KPT-9274, a dual inhibitor of PAK4 and NAMPT, in patients with advanced solid malignancies
      (including sarcoma, colon, lung, melanoma, etc.) or NHL for which all standard therapeutic
      options considered useful by the investigator have been exhausted.
    

Trial Arms

NameTypeDescriptionInterventions
KPT-9274Experimental[CLOSED TO ENROLLMENT] Oral KPT-9274 three times a week every other day (Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26) during each 28 day cycle.
  • KPT-9274
KPT-9274 & Niacin Extended Release (ER)Experimental[CLOSED TO ENROLLMENT] 500 mg niacin ER co-administered with each dose of oral KPT-9274 three times a week every other day (Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26) during each 28 day cycle.
  • KPT-9274
  • Niacin ER
KPT-9274 + NivolumabExperimentalPart C: Oral KPT-9274 administered Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26) during each 28 day cycle Nivolumab 480 mg IV administered Day 1 during each 28 day cycle.
  • KPT-9274
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet all of the following inclusion criteria to be eligible to enroll in this
        study.

          1. Must have objective and measurable melanoma by RECIST 1.1 after disease progression on
             a prior anti-PD-1 or anti-PD-L1 therapy.

          2. ECOG performance status of ≤ 2

          3. Life expectancy of ≥ 3 months.

          4. Adequate hepatic function:

               -  Total bilirubin < 1.5 times the ULN (except patients with Gilbert's syndrome
                  [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3
                  times ULN),

               -  AST and ALT ≤ 2.5 times ULN (except patients with known liver involvement of
                  their advanced solid malignancy who must have an AST and ALT ≤ 5.0 times ULN).

          5. Adequate renal function:

               -  Estimated creatinine clearance of ≥ 60 mL/min, calculated using the formula of
                  Cockroft and Gault (140-Age) Mass (kg)/(72 creatinine mg/dL); multiply by 0.85 if
                  female.

          6. Adequate hematopoietic function:

               -  Total WBC count ≥ 1500/mm³, ANC ≥ 1000/mm³, Hb ≥ 10.0 g/dL, platelet count ≥
                  100,000/mm³

        Exclusion Criteria:

        Patients meeting any of the following exclusion criteria are not eligible to enroll in this
        study.

          1. ≤ 2 weeks since the last prior therapeutic regimen for melanoma. Palliative steroids
             for disease related symptoms < 7 days prior to C1D1, unless physiologic doses of
             steroids are used.

          2. Have not recovered or stabilized (Gr 1 or to their baseline for non-hematologic
             toxicities, ≤ Gr 2 or to their baseline for hematologic toxicities) from toxicities
             related to their previous treatment except for alopecia. In specific cases, patients
             with Gr 2 non-hematologic toxicities will be allowed following approval by the
             Karyopharm medical monitor.

          3. Untreated CNS disease or leptomeningeal involvement are excluded. Patients without
             active brain or leptomeningeal metastases after prior treatment with local therapies
             are eligible provided that the treatment had been done ≥ 2 weeks prior to enrollment.

          4. Active infection with completion of therapeutic antibiotics, antivirals, or
             antifungals within one week prior to C1D1. Prophylactic antibiotics, antivirals or
             antifungals are permitted.

          5. Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting
             or diarrhea that could interfere with the absorption of KPT-9274.

          6. Active peptic ulcer disease or other active gastrointestinal bleeds.

          7. Requiring treatment with corticosteroids at doses higher than substitute therapy (> 10
             mg prednisone), are unstable with substitute hormonal therapy, or are deemed to be
             likely to re-occur by the treating physician when administered nivolumab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) for KPT-9274 administered alone and with co-administration of niacin ER (extended release) (vitamin B3/nicotinic acid)
Time Frame:Approximately 4 weeks
Safety Issue:
Description:Parts A & B: MTD will be based on the assessment of dose limiting toxicities (DLTs) during the first cycle of therapy and will be defined as the highest dose at which ≤1 patient experiences DLTs within Cycle 1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Karyopharm Therapeutics Inc

Trial Keywords

  • PAK4
  • KPT-9274
  • Karyopharm
  • NHL
  • solid tumors
  • NAMPT
  • Melanoma

Last Updated

May 2, 2020