Hepatocellular CarcinomaPhase 1HIPANIVNCT04823403
Hepatic Intra-Arterial Administration of Ipilimumab in Combination With Intra-venous Nivolumab for Advanced Hepatocellular Carcinoma
A Phase 1 study testing Nivolumab and Ipilimumab in people with Hepatocellular Carcinoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
Trial summary
To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase. 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 Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteFrance
- Study dates
- 13 Nov 2020to Nov 2024
- 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
- Adult Men and women ≥ 18 years old
- Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
- Patient should be able to comply with treatment, PK, and pharmacodynamic sample collection and willing to comply with study visits and procedures as per protocol.
- Patients must have pathological confirmation of HCC.
- Patient should be considered as non resectable by Multidisciplinary Team and liver surgeon, and non-eligible for liver transplantation (advanced HCC, BCLC C).
- Patient who progresses on, or is intolerant to, or has refused standard first line therapy and eligible for receiving IV infusion of Nivolumab and HIA administration of Ipilimumab
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- Patient with active intrahepatic HCC. Part of the disease should not have undergone local treatments (including chemoembolization, or percutaneous targeted therapies).
- Patients with or without active viral infection (i.e., HCV, HBV) are eligible. Patients with active HBV/HCV are eligible provided they are adequately treated to control the disease.
- Patients should have measurable disease as defined by mRECIST criteria for response assessment.
- ECOG status of 0 or 1 (Appendix 2).
- Life expectancy of ≥ 12 weeks at the time of informed consent per Investigator assessment.
- Adequate organ function as defined by the following:
- White blood cells (WBCs) ≥ 2000/mL
- Neutrophils ≥ 1000/mL
- Platelets ≥ 75 × 103/mL
- Hemoglobin ≥ 8.0 g/dL
- Creatinine < 1.5 × ULN or creatinine clearance ≥ 40mL/min (Cockcroft-Gault formula)
- ALT and AST ≤ 3 × ULN or < 5 x ULN in case of liver metastasis
- Lipase and amylase ≤ 1.5 × ULN
- Total bilirubin ≤ 1.5 × ULN
- Normal thyroid function, or stable on hormone supplementation per investigator assessment
- Child-Pugh A, Without history of encephalopathy or clinically significant ascites
- Women of childbearing potential (WOCBP) must have a negative urine or serum β-HCG pregnancy test within 14 days prior inclusion. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Sexually active female patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 5 months after last study drug administration or must refrain from heterosexual activity during this same period.
- Sexually active males patients must agree to use condom during the study and for at least 7 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception for the same duration.
- Patients shall be eligible to undergo pre-treatment and on-treatment tumor biopsies. Patients who either do not consent to a pre-treatment tumor biopsy or do not have accessible lesions will not be eligible.
- Resolved acute effects of any prior therapy to baseline severity or NCI CTCAE v5 Grade ≤1 except for AEs not constituting a safety risk by investigator judgment.
- Patients must be affiliated to a social security system or beneficiary of the same
Who cannot join
- Patients with a prior malignancy are excluded, except those with prior malignancies treated more than 2 years previously (at the time of informed consent) with curative intent with no evidence of disease during the interval and who are considered by the Investigator to present a low risk for recurrence, will be eligible.
- Patients with any active autoimmune disease or history of known or suspected autoimmune disease with the exception of patients with vitiligo, resolved/controlled asthma/atopy, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave-Basedow"s disease (patients with controlled hyperthyroidism must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to inclusion).
- A known or underlying medical condition that, in the opinion of the Investigator, could make the administration of study drug hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate study.
- Requirement for daily supplemental oxygen
- Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
- A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
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- Positive blood screen for human immunodeficiency virus (HIV) with acquired immunodeficiency syndrome (AIDS). Patients with controlled HIV infection under anti-retroviral therapy and normal CD4+ T-cell counts (>500/mm3) could be considered eligible by the investigator if the patient fulfills the other inclusion/exclusion criteria.
- Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days prior to inclusion.
- Any other significant acute or chronic medical illness. Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
- Subjects who are unable to undergo and/or tolerate venous AND arterial access (evaluated on pre-treatment imaging)
- Systemic or topical corticosteroids at immunosuppressive doses (≥ 10 mg/day of prednisone or equivalent)
- Patients that have received within 4 weeks or 5 half-lives (whichever is shorter) from inclusion and who are planned to receive the following during treatment:
- Any other investigational drug
- Any anticancer therapy (chemotherapy, biologics, therapeutic vaccines, radiotherapy, or hormonal treatment).
- Vaccines containing live virus
- Allergen hyposensitization therapy
- Growth factors, e.g., granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin
- Major surgery
- Bisphosphonates or anti-RANKL therapy
- Previous allogeneic hematopoietic stem cell transplantation or previous solid organ transplantation requiring systemic immunosuppressive therapy
- History of severe allergy, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or to biopharmaceutical produced in Chinese hamster ovarian cells or to any components of the study drugs
- Patients with an active pneumonitis or a history of grade 3 or 4 pneumonitis due to the administration of immunotherapies.
- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
- Pregnant or breastfeeding women
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Gustave Roussy
Villejuif, 94800
Lambros Tselikas, MD, +33 (0)1 42 11 42 11, lambros.tselikas@gustaveroussy.fr
About this study
Official title: A Phase I Study Evaluating Safety and Efficacy of Hepatic Intra-Arterial Administration of Ipilimumab in Combination With Intra-venous Nivolumab for Advanced Hepatocellular Carcinoma
To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Nivolumab, Ipilimumab
- 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
Intravenous Nivolumab (1mg/kg) will be given every 6 weeks for a maximal period of 6 months within the study.
IpilimumabDrug
Ipilimumab, single intra-arterial (IA) injection per patient, at 3 dose-levels*.
- (D1) Starting dose : 50 mg; n=3 to 6
- (D2) 2nd dose-level : 100 mg; n=3 to 6
- (D3) Maximal tested dose : 150mg; n=3 to 6 (if no limiting toxicities) *Dose level (D-1) : 25 mg will be tested if de-escalation is needed at D1 (>1/3 DLT at D1)
| Study group | Role | What they receive |
|---|---|---|
| Patients with hepatocellular carcinoma | Experimental | 1. Intravenous Nivolumab (1mg/kg) will be given every 6 weeks for a maximal period of 6 months within the study.
2. Ipilimumab, single intra-arterial (IA) injection per patient, at 3 dose-levels*.
* (D1) Starting dose : 50 mg; n=3 to 6
* (D2) 2nd dose-level : 100 mg; n=3 to 6
* (D3) Maximal tested dose : 150mg; n=3 to 6 (if no limiting toxicities) *Dose level (D-1) : 25 mg will be tested if de-escalation is needed at D1 (>1/3 DLT at D1) Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start13 Nov 2020
- Primary completion4 Nov 2022
- Study completionNov 2024 (estimated)
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 Gustave Roussy, Cancer Campus, Grand ParisThe 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
- Phase 1, Dose-Escalation (3+3 design), Open-label, single arm, single-center study, and expansion cohort. DLT will be captured within 1 month after HIA administration. 3 levels of dose of HIA ipilimumab will be tested. Starting by a dose 5 times lower than what is used for IV administration.
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04823403
- Sponsor's protocol ID
- 2020-003766-40
- Other IDs
- 2020/3138
- Acronym
- HIPANIV
- Status last verified
- Jul 2024
- First submitted
- 29 Mar 2021
- Last updated
- 26 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating Safety and Efficacy of Hepatic Intra-Arterial Administration of Ipilimumab in Combination With Intra-venous Nivolumab for Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04823403
- Acronym / sponsor ID
- HIPANIV / 2020-003766-40
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 4 Nov 2022 (actual)
- Study completion
- Nov 2024 (estimated)
- First posted
- 30 Mar 2021 (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.
To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 1, Dose-Escalation (3+3 design), Open-label, single arm, single-center study, and expansion cohort. DLT will be captured within 1 month after HIA administration. 3 levels of dose of HIA ipilimumab will be tested. Starting by a dose 5 times lower than what is used for IV administration.
| Arm | Type | Receives |
|---|---|---|
| Patients with hepatocellular carcinoma | Experimental | Drug: Nivolumab, Drug: Ipilimumab1. Intravenous Nivolumab (1mg/kg) will be given every 6 weeks for a maximal period of 6 months within the study. 2. Ipilimumab, single intra-arterial (IA) injection per patient, at 3 dose-levels*. * (D1) Starting dose : 50 mg; n=3 to 6 * (D2) 2nd dose-level : 100 mg; n=3 to 6 * (D3) Maximal tested dose : 150mg; n=3 to 6 (if no limiting toxicities) *Dose level (D-1) : 25 mg will be tested if de-escalation is needed at D1 (>1/3 DLT at D1) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Adult Men and women ≥ 18 years old
- Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
- Patient should be able to comply with treatment, PK, and pharmacodynamic sample collection and willing to comply with study visits and procedures as per protocol.
- Patients must have pathological confirmation of HCC.
- Patient should be considered as non resectable by Multidisciplinary Team and liver surgeon, and non-eligible for liver transplantation (advanced HCC, BCLC C).
Key exclusion criteria (24 listed)
- Patients with a prior malignancy are excluded, except those with prior malignancies treated more than 2 years previously (at the time of informed consent) with curative intent with no evidence of disease during the interval and who are considered by the Investigator to present a low risk for recurrence, will be eligible.
- Patients with any active autoimmune disease or history of known or suspected autoimmune disease with the exception of patients with vitiligo, resolved/controlled asthma/atopy, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave-Basedow"s disease (patients with controlled hyperthyroidism must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to inclusion).
- A known or underlying medical condition that, in the opinion of the Investigator, could make the administration of study drug hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate study.
- Requirement for daily supplemental oxygen
- Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
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 |
|---|---|---|
| NivolumabIntravenous Nivolumab (1mg/kg) will be given every 6 weeks for a maximal period of 6 months within the study. | Drug | Patients with hepatocellular carcinoma |
| IpilimumabIpilimumab, single intra-arterial (IA) injection per patient, at 3 dose-levels*. * (D1) Starting dose : 50 mg; n=3 to 6 * (D2) 2nd dose-level : 100 mg; n=3 to 6 * (D3) Maximal tested dose : 150mg; n=3 to 6 (if no limiting toxicities) *Dose level (D-1) : 25 mg will be tested if de-escalation is needed at D1 (>1/3 DLT at D1) | Drug | Patients with hepatocellular carcinoma |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 28 days
To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
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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.
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 Ipilimumab in people with Hepatocellular Carcinoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
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 27 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 26 Jul 2024. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lambros Tselikas, MD (+33 (0)1 42 11 42 11, lambros.tselikas@gustaveroussy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: 28 days). 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 26 Jul 2024.