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Trial record 1 of 2 for:    KPT-9274
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PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA) (PANAMA)

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ClinicalTrials.gov Identifier: NCT02702492
Recruitment Status : Recruiting
First Posted : March 8, 2016
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

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).

Condition or disease Intervention/treatment Phase
NHL Solid Tumors Drug: KPT-9274 Drug: Niacin ER Drug: Nivolumab 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 175 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 : June 2016
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: KPT-9274

[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)

[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 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.

Drug: KPT-9274
Drug: Nivolumab
Other Name: Opdivo®




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) [ Time Frame: 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 patient experiences DLTs within Cycle 1.

  2. Maximum tolerated dose (MTD) for KPT-9274 co-administered with nivolumab [ Time Frame: 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 patient experiences DLTs within Cycle 1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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): NCT02702492


Contacts
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Contact: Jatin Shah, MD jshah@karyopharm.com
Contact: Sharon Shacham, PhD sshacham@karyopharm.com

Locations
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United States, California
UCLA Health Not yet recruiting
Los Angeles, California, United States, 90024
Contact: Antoni Ribas, MD       aribas@mednet.ucla.edu   
Principal Investigator: Antoni Ribas, MD         
United States, Colorado
University of Colorado Cancer Center Completed
Aurora, Colorado, United States, 80045
United States, District of Columbia
Georgetown University, Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Ann Granza, MD       ann.w.gramza@georgetown.edu   
Principal Investigator: Ann Granza, MD         
United States, Minnesota
Mayo Clinic Rochester Completed
Rochester, Minnesota, United States, 55905
United States, New York
NYU-Laura & Isaac Perlmutter Cancer Center Recruiting
New York, New York, United States, 100016
Contact: Daniel Cho    212-731-5871    daniel.cho@nyumc.org   
Principal Investigator: Daniel Cho, MD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Jordan Berlin, MD         
Contact       Jordan.Berlin@vanderbilt.edu   
Principal Investigator: Jordan Berlin, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Aung Naing    713-563-0803    anaing@mdanderson.org   
Principal Investigator: Aung Naing, MD         
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Albiruni Razak, MB, BCh    416-586-4800 ext 3883      
Principal Investigator: Albiruni Razak, MB, Bch         
Sponsors and Collaborators
Karyopharm Therapeutics Inc
Investigators
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Study Director: Jatin Shah, MD Karyopharm Therapeutics Inc
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT02702492    
Other Study ID Numbers: KCP-9274-901
First Posted: March 8, 2016    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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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:
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Neoplasms
Niacin
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs