Clincosm LogoSign in Get a demo

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

Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Terminated
CT.gov ID
NCT02702492
Collaborator
(none)
60
Enrollment
8
Locations
3
Arms
60
Actual Duration (Months)
7.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 1, 2016
Actual Primary Completion Date :
Feb 1, 2021
Actual Study Completion Date :
Jun 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: KPT-9274

Part A: [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.

Drug: KPT-9274
Experimental: KPT-9274 & Niacin Extended Release (ER)

Part B:[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.

Drug: KPT-9274

Drug: Niacin ER
Experimental: KPT-9274 + Nivolumab

Part C: 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. Nivolumab 480 mg IV administered Day 1 during each 28 day cycle.

Drug: KPT-9274

Drug: Nivolumab
Other Names:
  • Opdivo®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum tolerated dose (MTD) for KPT-9274 administered alone and with co-administration of niacin ER (extended release) (vitamin B3/nicotinic acid) [Approximately 4 weeks]

      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 participant out of 6 (or 0 out of 3) experiences DLTs within Cycle 1.

    2. Maximum tolerated dose (MTD) for KPT-9274 co-administered with nivolumab [Approximately 4 weeks]

      Part C: 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 participant out of 6 (or 0 out of 3) experiences DLTs within Cycle 1.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

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

    1. Should have unresectable advanced, recurrent or metastatic melanoma and 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 participants 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 participants with known liver involvement of their advanced solid malignancy who must have an AST and ALT ≤ 5.0 times ULN).

    1. 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.
    1. Adequate hematopoietic function:
    • Total WBC count ≥ 1500/mm³, ANC ≥ 1000/mm³, Hb ≥ 10.0 g/dL, platelet count ≥ 100,000/mm³
    Exclusion Criteria:

    Participants 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.

    3. Untreated CNS disease or leptomeningeal involvement are excluded. Participants 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Health Los Angeles California United States 90024
    2 University of Colorado Cancer Center Aurora Colorado United States 80045
    3 Georgetown University, Lombardi Comprehensive Cancer Center Washington District of Columbia United States 20007
    4 Mayo Clinic Rochester Rochester Minnesota United States 55905
    5 NYU-Laura & Isaac Perlmutter Cancer Center New York New York United States 100016
    6 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232
    7 MD Anderson Cancer Center Houston Texas United States 77030
    8 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9

    Sponsors and Collaborators

    • Karyopharm Therapeutics Inc

    Investigators

    • Study Director: Jatin Shah, MD, Karyopharm Therapeutics Inc

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT02702492
    Other Study ID Numbers:
    • KCP-9274-901
    First Posted:
    Mar 8, 2016
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Karyopharm Therapeutics Inc
    PAK4
    KPT-9274
    Karyopharm
    NHL
    Solid Tumors
    NAMPT
    Melanoma
    Additional relevant MeSH terms:
    Neoplasms
    Niacin
    Nivolumab

    Study Results

    No Results Posted as of Jun 25, 2021