PAC-1 for Treatment of Refractory, Metastatic Kidney Cancer

NCT03927248 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: REN-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• To determine activity of PAC-1 and nivolumab

  Assess by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

  12 months

Secondary Outcomes (2)

• to evaluate the safety profile of nivolumab in combination with PAC-1.

  12 months

• To measure 3- and 6-months progression-free survival (PFS) rate.

  12 months

Study Arms (1)

Nivolumab and PAC-1

EXPERIMENTAL

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

Interventions

Nivolumab DRUG

See description in Arms/Groups section

Also known as: PAC-1

Nivolumab and PAC-1

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Histologically or cytologically confirmed renal cell carcinoma.
• Stage IV disease progressing on prior immune checkpoint inhibitor therapy
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1).
• Patients must have anticipated life expectancy greater than 3 months.
• 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.
• Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.
• 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).
• 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.
• 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.
• Required Initial Laboratory Values (tested within 2 weeks prior to registration):
• Leukocytes ≥2000/ μl
• Hemoglobin \>9.0 g/dL

You may not qualify if:

• 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.
• 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.
• Active hepatitis B or hepatitis C infection.
• History of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• New York Heart Association class III or IV congestive heart failure.
• Corrected QT interval calculated by Fridericia formula (QTcF) \> 500 ms within 14 days registration.
• 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.
• Active infection requiring intravenous systemic treatment.
• History of organ transplant.
• Inability to swallow intact tablets.

Sponsors & Collaborators

• HealthPartners Institute: lead

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Peter Hurley, MD

  HealthPartners Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 25, 2019
• Study Start: September 1, 2020
• Primary Completion: September 1, 2021
• Study Completion: December 1, 2021
• Last Updated: May 7, 2020

Record last verified: 2020-04