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PAC-1 for Treatment of Refractory, Metastatic Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03927248
Recruitment Status : Not yet recruiting
First Posted : April 25, 2019
Last Update Posted : October 17, 2019
Information provided by (Responsible Party):
HealthPartners Institute

Tracking Information
First Submitted Date  ICMJE April 23, 2019
First Posted Date  ICMJE April 25, 2019
Last Update Posted Date October 17, 2019
Estimated Study Start Date  ICMJE February 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
To determine activity of PAC-1 and nivolumab [ Time Frame: 12 months ]
Assess by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03927248 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • to evaluate the safety profile of nivolumab in combination with PAC-1. [ Time Frame: 12 months ]
    Toxicities will be defined according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
  • To measure 3- and 6-months progression-free survival (PFS) rate. [ Time Frame: 12 months ]
    PFS will be determined by using RECIST 1.1.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE PAC-1 for Treatment of Refractory, Metastatic Kidney Cancer
Official Title  ICMJE Pilot Study of Nivolumab and Procaspase Activating Compound-1 (PAC-1) for
Brief Summary The primary objective of the pilot study is to determine activity of PAC-1 and nivolumab combination in subjects with metastatic renal cell carcinoma previously treated with immune checkpoint inhibitor therapy as assessed by objective response rate (ORR) using RECIST 1.1 criteria.
Detailed Description

PAC-1 in combination with nivolumab: The MTD will be determined using a modified-Fibonacci dose-escalation 3+3 design.

This pilot study will evaluate nivolumab in combination with PAC-1 in subjects with metastatic RCC. Nivolumab will be delivered by IV infusion on Day 1 and PAC-1 will be taken orally on Days 1-28 of each 28-day cycle, and response will be evaluated after every 2 cycles. Treatment will continue until disease progression (based on RECIST 1.1 criteria), unacceptable toxicity, subject refusal, or subject death either from progression of disease, the therapy itself, or from other causes. Subjects who voluntarily stop the study, have progressive disease, or unacceptable toxicities will be followed for survival every 3 months for 12 months from start of study medication

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Renal Cell Carcinoma
Intervention  ICMJE Drug: Nivolumab
See description in Arms/Groups section
Other Name: PAC-1
Study Arms  ICMJE Experimental: Nivolumab and PAC-1
Patient will be accrued and started on dose 1 level of PAC-1 (500 mg). If no DLT is observed in first cycle of therapy (28 days), dose of PAC-1 will be escalated to 625 mg in second cycle of therapy for the same patient. If patient remains on study and has no dose limiting toxicities, then in third cycle, dose will be escalated to 750 mg and continue in following cycles, if no dose adjustment is needed because of toxicities. Nivolumab will be administered by IV infusion at a dose of 480 mg.
Intervention: Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥18 years.
  2. Histologically or cytologically confirmed renal cell carcinoma.
  3. Stage IV disease progressing on prior immune checkpoint inhibitor therapy
  4. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1).
  5. Patients must have anticipated life expectancy greater than 3 months.
  6. Patients must have measurable disease as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥10mm with spiral CT scan by RECIST version 1.1 criteria. Baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration.
  7. Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.
  8. Patient with known brain metastases must have been treated at least 2 weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (>or = 10 mg prednisone daily or equivalent).
  9. Women must not be pregnant and breast-feeding.

    • All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
    • Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses > 1 year.
  10. Male patients who are sexually active with WOCBP must agree to use an adequate method of contraception or abstain from sexual intercourse for at least one week prior to starting with the first dose of study therapy through 7 months after the last dose of study therapy.
  11. Required Initial Laboratory Values (tested within 2 weeks prior to registration):

    • Leukocytes ≥2000/ μl
    • Hemoglobin >9.0 g/dL
    • Platelets ≥100,000/ μl
    • ANC ≥1,500/ μl
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):

      • Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
      • Male CrCl = (140 - age in years) x weight in kg x 1.00
    • Total Bilirubin <1.5 mg/dl (except for subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dl)
    • SGOT (AST) <2.5 x ULN
    • ALP <2.5 x ULN in absence of liver metastases (<5 x ULN if liver metastases present
    • PTT <1.5 x ULN
  12. The participant is capable of understanding and complying with the protocol and has signed informed consent document.

Exclusion Criteria

  1. Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  2. Condition requiring systemic treatment with either corticosteroids (> or=10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence or active autoimmune disease.
  3. Active hepatitis B or hepatitis C infection.
  4. History of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  5. New York Heart Association class III or IV congestive heart failure.
  6. Corrected QT interval calculated by Fridericia formula (QTcF) > 500 ms within 14 days registration.
  7. Cardiovascular disorders including unstable angina pectoris, clinically-significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months prior to registration.
  8. Active infection requiring intravenous systemic treatment.
  9. History of organ transplant.
  10. Inability to swallow intact tablets.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa Wahowske, RN 651-254-1517
Contact: Joanna Hill 651-254-2845
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03927248
Other Study ID Numbers  ICMJE REN-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party HealthPartners Institute
Study Sponsor  ICMJE HealthPartners Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Hurley, MD HealthPartners Institute
PRS Account HealthPartners Institute
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP