Renal Cell CarcinomaPhase 1/2NCT02989714
Phase Ib/II Trial of Interleukin-2 and PD-1 Checkpoint Inhibitor, Nivolumab In Metastatic Clear Cell Renal Cell Cancer
A Phase 1/2 study testing Interleukin-2 and Nivolumab in people with Renal Cell Carcinoma, run by University of Michigan Rogel Cancer Center at 4 sites in United States.
Trial summary
This will be a single arm, multi-site phase Ib/II clinical trial of standard doses of High Dose Interleukin-2 (HD IL2) (600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart) in IL-2 eligible clear cell metastatic RCC (Renal Cell Carcinoma) subjects in combination with Nivolumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Interleukin-2 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 4 sitesUnited States
- Study dates
- 16 Mar 2017to 23 Jun 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have a histologic diagnosis of clear cell renal cell carcinoma (pure or mixed) with radiologic or histologic or cytologic evidence of metastatic disease.
- Subjects may have received up to 2 prior lines of systemic therapy (excluding any neoadjuvant/adjuvant therapy) including anti-VEGF or VEGFR inhibitor (e.g. sorafenib, pazopanib, sunitinib, bevacizumab, axitinib) or mTOR inhibitor (e.g. everolimus or temsirolimus) for metastatic disease.
- Age ≥ 18 years at the time of consent.
- ECOG (Eastern Cooperative Oncology Group) performance status (an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) of 0 or 1
- Adequate organ and marrow function
- Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to prior to registration. Women of non-childbearing potential are defined as those who have no uterus, ligation of the fallopian tubes, or permanent cessation of ovarian function due to ovarian failure or surgical removal of the ovaries. All others are considered women of child bearing potential.
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- Females and males of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 months after treatment discontinuation.
- Subjects must have measurable disease on physical exam or imaging
- An archived tissue block with the subject's renal cell carcinoma must be identified prior to registration.
- Subjects must be considered appropriate candidates for HD IL-2 by one of the treating investigators listed on the protocol. HD IL-2 candidacy evaluation is per institutional guidelines at each site and should include a dobutamine stress echocardiogram or equivalent. Subjects with a positive stress test for cardiac ischemia would be excluded from this trial.
- No clinically significant infections or any other medical condition(s) that render the subject ineligible for high dose IL-2 therapy as judged by the treating investigator.
- Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- Prior interferon or interleukin-2 therapy is NOT allowed.
- Prior anti-PD-1/PD-L1 targeted therapy is NOT allowed. Prior CTLA-4 therapy or CD40/CD40L targeted therapy is allowed.
- Prior systemic treatment must be completed at least 14 calendar days prior to registration and the subject must have recovered from the toxicities of treatment to grade 1 or better.
- Prior radiation therapy is allowed if completed at least 14 calendar days prior to registration.
- Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to registration.
- No prior or concurrent malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years.
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- Current untreated brain metastasi(e)s. If treated history of CNS (central nervous system) metastases, should have completed radiation or surgery at least 12 weeks prior and off systemic corticosteroids.
- Autoimmune diseases such as rheumatoid arthritis are NOT allowed. Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed.
- Medical need for systemic corticosteroids >10mg prednisone daily or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate) Topical and inhaled corticosteroids are allowed if medically needed.
- History of allergic reaction to interleukin-2 or nivolumab
- Prior history of psychiatric disorder or seizure disorders which could be exacerbated by Interleukin-2 as judged by the treating investigator. 3.2.12 Evidence of significant cardiovascular disease including history of recent (< 6 months prior) myocardial infarction, congestive heart failure, primary cardiac arrhythmias (not due to electrolyte disorder or drug toxicity, for example) beyond occasional PVC's (premature ventricular contractions), angina, positive low-level stress test, or cerebrovascular accident. All patients should have baseline pulmonary function tests. Adequate pulmonary function should be documented (FEV1 >2 liters or ≥75% of predicted for height and age) prior to initiating therapy.
- Any history of HIV or hepatitis B infection
- Any other medical or surgical condition or disease that, in the judgment of the treating physician, renders subject ineligible for High Dose Interleukin-2 therapy.
- Any history of organ allografts
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
University Hospitals Seidman Cancer Center
Cleveland, Ohio, 44106
Ohio State University
Columbus, Ohio, 43210
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
This will be a single arm, multi-site phase Ib/II clinical trial of standard doses of High Dose Interleukin-2 (HD IL2) (600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart) in IL-2 eligible clear cell metastatic RCC (Renal Cell Carcinoma) subjects in combination with Nivolumab.
Investigators hypothesize that concurrent PD-1 inhibition synergistically enhances the anti-tumor immune response to HD IL-2 in metastatic clear cell RCC. Investigators postulate that the combination of the two therapies would result in an increase in the overall response rate, complete response rate, and improved survival outcomes compared to either of the individual therapies.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Interleukin-2, 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.
Interleukin-2Drug
Also called High Dose Interleukin-2
600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart
NivolumabDrug
Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
| Study group | Role | What they receive |
|---|---|---|
| HD IL2 and Nivolumab | Experimental | Not described Receives: Drug: Interleukin-2; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Patients With Grade 3 and Grade 4 Adverse Events of Interest
This is the primary outcome for the Phase Ib portion of the trial. Events of interest are possibly immune-mediated and occur only after at least one dose of Nivolumab has been administered. Immune-mediated events of interest do not include those that are known to occur during high dose IL-2 monotherapy and are reversible. Grade assessed per CTCAE version 4.0.
Measured: 28 days from the first dose of Nivolumab
The Number of Patients That Respond to Treatment
This is the primary outcome for the Phase II portion of the trial. Includes complete response (CR) + partial response (PR), measured by computerized tomography (CT) or magnetic resonance imaging (MRI) scan and assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measured: 12 Weeks
Secondary outcomes (3)
Number of Grade 3-5 Adverse Events of Interest
Events of interest are possibly immune-mediated and occur only after at least one dose of Nivolumab has been administered. Immune-mediated events of interest do not include those that are known to occur during high dose IL-2 monotherapy and are reversible. Grade assessed per CTCAE version 4.0.
Measured: For the duration of the therapy plus 60 days post treatment
Overall Survival at 24 Months
Overall survival at 24 months following the first dose of study therapy; 24 month estimates were reported using the product limit method of Kaplan and Meier along with 95% confidence intervals.
Measured: 24 Months
Progression Free Survival (PFS) at 24 Months
PFS is defined as the time from start of study therapy with Nivolumab until progression or death; up to 24 months. Progressive disease is defined as At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2016 (estimated)
- Study start16 Mar 2017
- Primary completion25 Feb 2019
- Study completion23 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ajjai Alva, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02989714
- Sponsor's protocol ID
- UMCC 2016.103
- Other IDs
- HUM00120502
- Status last verified
- Jun 2021
- First submitted
- 8 Dec 2016
- Last updated
- 13 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Trial of Interleukin-2 and PD-1 Checkpoint Inhibitor, Nivolumab In Metastatic Clear Cell Renal Cell Cancer
- ClinicalTrials.gov ID
- NCT02989714
- Acronym / sponsor ID
- UMCC 2016.103
- Conditions
- Renal Cell Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 16 Mar 2017 (actual)
- Primary completion
- 25 Feb 2019 (actual)
- Study completion
- 23 Jun 2020 (actual)
- First posted
- 12 Dec 2016 (estimated)
- Results
- Posted 9 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a single arm, multi-site phase Ib/II clinical trial of standard doses of High Dose Interleukin-2 (HD IL2) (600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart) in IL-2 eligible clear cell metastatic RCC (Renal Cell Carcinoma) subjects in combination with Nivolumab.
Investigators hypothesize that concurrent PD-1 inhibition synergistically enhances the anti-tumor immune response to HD IL-2 in metastatic clear cell RCC. Investigators postulate that the combination of the two therapies would result in an increase in the overall response rate, complete response rate, and improved survival outcomes compared to either of the individual therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HD IL2 and Nivolumab | Experimental | Drug: Interleukin-2, Drug: Nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects must have a histologic diagnosis of clear cell renal cell carcinoma (pure or mixed) with radiologic or histologic or cytologic evidence of metastatic disease.
- Subjects may have received up to 2 prior lines of systemic therapy (excluding any neoadjuvant/adjuvant therapy) including anti-VEGF or VEGFR inhibitor (e.g. sorafenib, pazopanib, sunitinib, bevacizumab, axitinib) or mTOR inhibitor (e.g. everolimus or temsirolimus) for metastatic disease.
- Age ≥ 18 years at the time of consent.
- ECOG (Eastern Cooperative Oncology Group) performance status (an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) of 0 or 1
- Adequate organ and marrow function
Key exclusion criteria (14 listed)
- Prior interferon or interleukin-2 therapy is NOT allowed.
- Prior anti-PD-1/PD-L1 targeted therapy is NOT allowed. Prior CTLA-4 therapy or CD40/CD40L targeted therapy is allowed.
- Prior systemic treatment must be completed at least 14 calendar days prior to registration and the subject must have recovered from the toxicities of treatment to grade 1 or better.
- Prior radiation therapy is allowed if completed at least 14 calendar days prior to registration.
- Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to registration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interleukin-2Also: High Dose Interleukin-2600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart | Drug | HD IL2 and Nivolumab |
| NivolumabNivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression | Drug | HD IL2 and Nivolumab |
Primary outcome
The Number of Patients With Grade 3 and Grade 4 Adverse Events of Interest
Time frame: 28 days from the first dose of Nivolumab
This is the primary outcome for the Phase Ib portion of the trial. Events of interest are possibly immune-mediated and occur only after at least one dose of Nivolumab has been administered. Immune-mediated events of interest do not include those that are known to occur during high dose IL-2 monotherapy and are reversible. Grade assessed per CTCAE version 4.0.
The Number of Patients That Respond to Treatment
Time frame: 12 Weeks
This is the primary outcome for the Phase II portion of the trial. Includes complete response (CR) + partial response (PR), measured by computerized tomography (CT) or magnetic resonance imaging (MRI) scan and assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
3 secondary outcomes
Number of Grade 3-5 Adverse Events of Interest
Time frame: For the duration of the therapy plus 60 days post treatment
Overall Survival at 24 Months
Time frame: 24 Months
Progression Free Survival (PFS) at 24 Months
Time frame: 24 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ajjai Alva, M.D. principal investigator
University of Michigan Rogel Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Interleukin-2 and Nivolumab in people with Renal Cell Carcinoma, run by University of Michigan Rogel Cancer Center at 4 sites in United States.
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 12 inclusion and 14 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: finished, as of the sponsor's last update on 13 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Yes. Results are posted in the registry (first posted 9 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Patients With Grade 3 and Grade 4 Adverse Events of Interest (time frame: 28 days from the first dose of Nivolumab). The study lists 2 primary outcomes in all. 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 13 Jul 2021.