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PAC-1 for Treatment of Refractory, Metastatic Kidney Cancer

  • Clinicaltrials.gov identifier

    NCT03927248

  • Recruitment Status

    Withdrawn (funding issues)

  • First Posted

    April 25, 2019

  • Last update posted

    May 7, 2020

Study Description

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:Metastatic Renal Cell Carcinoma
  • Intervention/Treatment: Drug: Nivolumab
  • Phase: 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

Study Design

  • Study Type: Interventional
  • 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: September 2020
  • Estimated Primary Completion Date: September 2021
  • Estimated Study Completion Date: December 2021

Arms and interventions

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

Outcome Measures

  • 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.

Eligibility Criteria

  • Ages Eligible for Study: 18 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 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.

Contacts and Locations

Contacts

Locations

Sponsors and Collaborators

HealthPartners Institute

Investigators

Principal Investigator: Peter Hurley, MD HealthPartners Institute

More Information

  • 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: May 7, 2020
  • Last Verified: April 2020
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Carcinoma, Renal Cell