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Metastatic Renal Cell CarcinomaPhase 1/2NCT03927248

PAC-1 for Treatment of Refractory, Metastatic Kidney Cancer

A Phase 1/2 study testing Nivolumab in people with Metastatic Renal Cell Carcinoma, run by HealthPartners Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Sep 2020to Dec 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • 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
  • The participant is capable of understanding and complying with the protocol and has signed informed consent document.

Who cannot join

  • 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.
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  • 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.

About this study

Official title: Pilot Study of Nivolumab and Procaspase Activating Compound-1 (PAC-1) for

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.

Read the 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

Being tested
Nivolumab
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called PAC-1

    See description in Arms/Groups section

Study groups in NCT03927248
Study groupRoleWhat they receive
Nivolumab and PAC-1ExperimentalPatient 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.
Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 months

Secondary outcomes (2)
  1. to evaluate the safety profile of nivolumab in combination with PAC-1.

    Toxicities will be defined according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: 12 months

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

    PFS will be determined by using RECIST 1.1.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2019
  2. Study startSep 2020 (estimated)
  3. Primary completionSep 2021 (estimated)
  4. Study completionDec 2021 (estimated)

Why it stopped: funding issues

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03927248
Sponsor's protocol ID
REN-01
Status last verified
Apr 2020
First submitted
23 Apr 2019
Last updated
7 May 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab in people with Metastatic Renal Cell Carcinoma, run by HealthPartners Institute.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 7 May 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine activity of PAC-1 and nivolumab (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2020.

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