Hepatocellular CarcinomaPhase 1NUANCENCT03382886
Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
A Phase 1 study testing Nivolumab and Bevacizumab in people with Hepatocellular Carcinoma, run by University of Utah at 1 site in United States.
Trial summary
This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of the combination of nivolumab and bevacizumab. The study will use a 3+3 phase I study design using a fixed dose of nivolumab (240mg) and escalating doses of bevacizumab (1-10mg). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Nivolumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Apr 2018to 2 Jul 2019
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed unresectable or metastatic hepatocellular carcinoma. Confirmation either by histologic confirmation or accepted radiographic criteria.
- Received at least one line of therapy with a TKI (including, but not limited to sorafenib, lenvatinib, and/or regorafenib) with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with a TKI. No more than two lines of prior therapy are allowed.
- Measurable disease per RECIST1.1.
- Age ≥18 years.
- ECOG performance status of 0 to 1.
- Life expectancy ≥ 12 weeks.
Show all 12Show fewer
- Childs Pugh A (5-6 points). Demonstrate adequate organ function as defined in the table below
- Hematologic:
- Absolute neutrophil count (ANC) ≥ 1.5 k/µL. Platelets ≥ 100 k/µL Hemoglobin ≥ 9 g/dL
- Renal:
- Creatinine < 2 × ULN OR
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy.
- Subjects with a prior history of DVT/PE, who have not been on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks.
- History of arterial thromboembolic event in past 6 months (including CVA, MI).
- Systemic anti-cancer treatment within 2 weeks, all ongoing adverse events related to previous systemic anti-cancer therapy resolved to grade ≤1.
- Radiotherapy within 2 weeks of first dose of study medications.
- Major surgery within 6 weeks of first dose of study medications. Minor procedures (e.g. port placement, endoscopy with intervention) within 4 weeks of first dose of study medications.
Show all 19Show fewer
- Presence of ≥ CTCAE grade 2 toxicity due to prior cancer therapy (except alopecia, peripheral neuropathy which are excluded if ≥ CTCAE grade 3).
- Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication.
- Active ongoing infection requiring therapy.
- Active HIV infection.
- History of severe hypersensitivity reaction to another monoclonal antibody.
- Active central nervous system metastases and/or carcinomatous meningitis (stable treated brain metastases not requiring steroids >4 weeks allowed).
- Cardiac conditions: class 3-4 New York Heart Association congestive heart failure, known baseline LVEF < 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months.
- Any history of autoimmune disease requiring treatment in the past 5 years or felt to be at risk to reactivate autoimmune disease. Patients who are felt to no longer be at risk of activating a known autoimmune disease (e.g. type 1 diabetes, ulcerative colitis s/p complete colectomy, autoimmune thyroiditis s/p thyroidectomy or medical ablation, etc.) may be allowed to participate after discussion with the PI
- Pregnant, breast feeding, or planning to become pregnant.
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- Received any live vaccine within the last 30 days.
- Other malignancy requiring treatment in the prior 2 years with the exception of locally treated squamous or basal cell carcinoma.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase I Open Label Trial of a Combination of Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of the combination of nivolumab and bevacizumab. The study will use a 3+3 phase I study design using a fixed dose of nivolumab (240mg) and escalating doses of bevacizumab (1-10mg).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Nivolumab, Bevacizumab
- Keywords
- Advanced and/or metastatic
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO
Nivolumab will be administered as a 240mg IV infusion given once every two weeks (+/- 3 days).
Subjects will remain on study treatment for up to two years or until progression or excessive toxicity
BevacizumabDrug
Bevacizumab will be administered as an IV infusion from 1-10mg/kg in accordance with the appropriate subject cohort being examined as described below:
Dose level 1: 5 mg/kg intravenously once every two weeks Dose level 2: 10 mg/kg intravenously once every two weeks Dose level -1: 1 mg/kg intravenously once every two weeks
Dosing is based on actual body weight. There is no dose adjustment for obese or frail individuals. Dosing is recalculated if patient weight changes by more than 10% as reviewed by the principal investigator.
Subjects will remain on study treatment for up to two years or until progression or excessive toxicity
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab and bevacizumab, all patients | Experimental | Not described Receives: Drug: Nivolumab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events that occur
Investigate the safety and tolerability of 14-day cycles of nivolumab plus bevacizumab.
Adverse events will be collected for each subject that received the study treatment combination.
Measured: Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Dose Limiting Toxicities (DLT) will define subsequent subject accrual and dose escalation
Measured: The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient
Secondary outcomes (2)
Progression Free Survival (PFS)
To examine the effect of the study treatment combination on the rate of progression-free survival (PFS).
Subjects will have regular imaging scans to measure disease status and response will be defined by RECIST1.1.
Measured: 3 years after treatment stops
Overall Survival
To examine the effect of the study treatment combination on the rate of overall survival.
Measured: 3 years after treatment stops
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start11 Apr 2018
- Primary completion26 Jul 2018
- Study completion2 Jul 2019
Why it stopped: PI decided to terminate due to low/slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D)
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Glynn W Gilcrease, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03382886
- Sponsor's protocol ID
- HCI103945
- Acronym
- NUANCE
- Status last verified
- Dec 2019
- First submitted
- 19 Dec 2017
- Last updated
- 12 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open Label Trial of a Combination of Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03382886
- Acronym / sponsor ID
- NUANCE / HCI103945
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Advanced and/or metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI decided to terminate due to low/slow accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 11 Apr 2018 (actual)
- Primary completion
- 26 Jul 2018 (actual)
- Study completion
- 2 Jul 2019 (actual)
- First posted
- 26 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of the combination of nivolumab and bevacizumab. The study will use a 3+3 phase I study design using a fixed dose of nivolumab (240mg) and escalating doses of bevacizumab (1-10mg).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D)
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and bevacizumab, all patients | Experimental | Drug: Nivolumab, Drug: Bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Confirmed unresectable or metastatic hepatocellular carcinoma. Confirmation either by histologic confirmation or accepted radiographic criteria.
- Received at least one line of therapy with a TKI (including, but not limited to sorafenib, lenvatinib, and/or regorafenib) with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with a TKI. No more than two lines of prior therapy are allowed.
- Measurable disease per RECIST1.1.
- Age ≥18 years.
- ECOG performance status of 0 to 1.
Key exclusion criteria (19 listed)
- Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy.
- Subjects with a prior history of DVT/PE, who have not been on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks.
- History of arterial thromboembolic event in past 6 months (including CVA, MI).
- Systemic anti-cancer treatment within 2 weeks, all ongoing adverse events related to previous systemic anti-cancer therapy resolved to grade ≤1.
- Radiotherapy within 2 weeks of first dose of study medications.
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 |
|---|---|---|
| NivolumabAlso: OPDIVONivolumab will be administered as a 240mg IV infusion given once every two weeks (+/- 3 days). Subjects will remain on study treatment for up to two years or until progression or excessive toxicity | Drug | Nivolumab and bevacizumab, all patients |
| BevacizumabBevacizumab will be administered as an IV infusion from 1-10mg/kg in accordance with the appropriate subject cohort being examined as described below: Dose level 1: 5 mg/kg intravenously once every two weeks Dose level 2: 10 mg/kg intravenously once every two weeks Dose level -1: 1 mg/kg intravenously once every two weeks Dosing is based on actual body weight. There is no dose adjustment for obese or frail individuals. Dosing is recalculated if patient weight changes by more than 10% as reviewed by the principal investigator. Subjects will remain on study treatment for up to two years or until progression or excessive toxicity | Drug | Nivolumab and bevacizumab, all patients |
Primary outcome
Adverse Events that occur
Time frame: Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months
Investigate the safety and tolerability of 14-day cycles of nivolumab plus bevacizumab. Adverse events will be collected for each subject that received the study treatment combination.
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Time frame: The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Dose Limiting Toxicities (DLT) will define subsequent subject accrual and dose escalation
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: 3 years after treatment stops
Overall Survival
Time frame: 3 years after treatment stops
Results and safety
The study was stopped early (reason given: PI decided to terminate due to low/slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
Glynn W Gilcrease, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab and Bevacizumab in people with Hepatocellular Carcinoma, run by University of Utah at 1 site 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 19 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: stopped early, as of the sponsor's last update on 12 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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 stopped early (reason given: PI decided to terminate due to low/slow accrual). Results are not available in the source record.
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?
Adverse Events that occur (time frame: Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months). 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 12 Dec 2019.