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PAC-1 for Treatment of Refractory, Metastatic Kidney Cancer

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ClinicalTrials.gov Identifier: NCT03927248
Recruitment Status : Not yet recruiting
First Posted : April 25, 2019
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
HealthPartners Institute

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.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Drug: Nivolumab Phase 1 Phase 2

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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Nivolumab and Procaspase Activating Compound-1 (PAC-1) for
Estimated Study Start Date : February 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
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.
Drug: Nivolumab
See description in Arms/Groups section
Other Name: PAC-1




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. To measure 3- and 6-months progression-free survival (PFS) rate. [ Time Frame: 12 months ]
    PFS will be determined by using RECIST 1.1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03927248


Contacts
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Contact: Lisa Wahowske, RN 651-254-1517 Lisa.Wahowske@ParkNicollet.com
Contact: Joanna Hill 651-254-2845 Joanna.Hill@ParkNicollet.com

Sponsors and Collaborators
HealthPartners Institute
Investigators
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Principal Investigator: Peter Hurley, MD HealthPartners Institute

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Responsible Party: HealthPartners Institute
ClinicalTrials.gov Identifier: NCT03927248     History of Changes
Other Study ID Numbers: REN-01
First Posted: April 25, 2019    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents