HepatocarcinomaPhase 2ImmunocaboNCT04435977
Efficacy and Safety of Cabozantinib in Patients With Hepatocellular Carcinoma
A Phase 2 study testing Cabozantinib 60 MG in people with Hepatocarcinoma, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
This is an open-label, single-center, Phase II trial designed to estimate in terms of PFS the efficacy of cabozantinib, given as second- or third- line treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 antibodies. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hepatocarcinoma
- What is being tested?
- Cabozantinib 60 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteItaly
- Study dates
- 30 Jan 2020to Sep 2023
- Phase
- Phase 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted)
- A baseline tumor tissue (newly obtained) available at screening is optional. Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines and requirements for such procedure. Biopsy cannot be performed less than ten days before treatment start.
- The subject has disease that is not amenable to a locoregional treatment approach (eg, transplant, surgery, radiofrequency ablation, TACE)
- Patients must have documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic), the last of which includes immune checkpoint inhibitors. Alternatively, eligible patients may have experienced an immune-related, requiring treatment discontinuation.
- Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically not significant and/or stable on supportive therapy
- Age ≥ 18 years old on the day of consent
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- ECOG performance status of 0 or 1 (See Appendix V)
- Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before treatment beginning:
- a. absolute neutrophil count (ANC) ≥ 1200/mm3 (≥ 1.2 x 109/L)
- b. platelets ≥ 60,000/mm3 (≥ 60 x 109/L)
- c. hemoglobin ≥ 8 g/dL (≥ 80 g/L)
- Adequate renal function, based upon meeting the following laboratory criteria: serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation: (140 - age) x weight (kg)/(serum creatinine × 72 [mg/dL]) for males. (For females multiply by 0.85)
- Child-Pugh Score of A (See Appendix IV)
- Total bilirubin ≤ 2 mg/dL within 7 days before treatment start
- Serum albumin ≥ 2.8 g/dL (≥ 28 g/L) within 7 days before treatment start
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5.0 upper limit of normal (ULN)
- Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
- Capable of understanding and complying with the protocol requirements and signed informed consent
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
- Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression, low body weight, or other reasons
Who cannot join
- Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
- Child-Pugh score of B or C
- Any type of anticancer agent (including investigational) within 2 weeks before treatment start
- Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of treatment start. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy
- Prior cabozantinib treatment
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before treatment start. Eligible subjects must be without corticosteroid treatment at the time of treatment start
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- Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low-dose LMWH are permitted
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- a. Cardiovascular disorders including:
- i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
- ii. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment
- iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before treatment start.
- iv. Thromboembolic event within 3 months before treatment start. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible
- b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
- i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
- ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before treatment start
- Note: Complete healing of an intra-abdominal abscess must be confirmed prior to treatment start
- c. Major surgery within 2 months before treatment start. Complete healing from major surgery must have occurred 1 month before treatment start. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before treatment start. Subjects with clinically relevant complications from prior surgery are not eligible
- d. Cavitating pulmonary lesion(s) or endobronchial disease
- e. Lesion invading a major blood vessel including, but not limited to: inferior vena cava, pulmonary artery, or aorta. Subjects with lesions invading the portal vasculature are eligible
- f. Clinically significant bleeding risk including the following within 3 months of treatment start: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors
- g. Other clinically significant disorders such as:
- i. Active infection requiring systemic treatment, known infection with human immunodeficiency virus (HIV), or known acquired immunodeficiency syndrome (AIDS)-related illness. Subjects with active hepatitis virus infection controlled with antiviral therapy are eligible
- ii. Serious non-healing wound/ulcer/bone fracture
- iii. Malabsorption syndrome
- iv. Uncompensated/symptomatic hypothyroidism
- v. Requirement for hemodialysis or peritoneal dialysis
- vi. History of solid organ transplantation
- vii. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to institutional standards)
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Clinico Humanitas
Rozzano, Milano, 20089
Lorenza Rimassa, MD, 02 8224 ext. 4573, lorenza.rimassa@humanitas.it
Nicola Personeni, MD, 02 8224 ext. 4516, nicola.personeni@humanitas.it
About this study
Official title: Efficacy and Safety of Cabozantinib in Patients With Hepatocellular Carcinoma Progressing on or Intolerant to Prior Treatment With Immune Checkpoint Inhibitors: A Phase II Study (Immunocabo)
This is an open-label, single-center, Phase II trial designed to estimate in terms of PFS the efficacy of cabozantinib, given as second- or third- line treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 antibodies.
Read the detailed description
Subjects who meet all study eligibility criteria will take tablets containing 60 mg of cabozantinib once daily orally. Required dose reductions will be in decrements of 20 mg cabozantinib (maximum two dose reductions).
Subjects will receive study treatment as long as they continue to experience clinical benefit in the opinion of the investigator or until there is unacceptable toxicity.
Primary objective of this study is to evaluate the efficacy of cabozantinib, given as second- or third-line treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors.
Secondary objectives for this study are as follows:
- To evaluate the activity of cabozantinib, in terms of ORR (CR+PR) as per RECIST 1.1, duration of response, time to treatment failure (TTF), time to progression (TTP), and OS
- To evaluate the safety and tolerability of cabozantinib
- Conditions
- Hepatocarcinoma
- Being tested
- Cabozantinib 60 MG
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabozantinib 60 MGDrug
- The assigned dose for study treatment is 60 mg qd. Two dose reductions will be permitted (Table 2):
- 60 mg qd to 40 mg qd (level 1)
- 40 mg qd to 20 mg qd (level 2)
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | Drug: Cabozantinib Subjects who meet all study eligibility criteria will take tablets containing 60 mg of cabozantinib once daily orally. Required dose reductions will be in decrements of 20 mg cabozantinib (maximum two dose reductions). Receives: Drug: Cabozantinib 60 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
PFS on cabozantinib treatment (considering as PFS events: clinical or radiological progressive disease, per RECIST 1.1, or death).
Measured: through study completion, an average of 1 year
Secondary outcomes (2)
ORR
ORR as per RECIST 1.1, duration of response, TTF, TTP, and OS.
Measured: through study completion, an average of 1 year
safety and tolerability
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2020
- Study start30 Jan 2020
- Primary completionJun 2023 (estimated)
- Study completionSep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HepatocarcinomaStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group assignement
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lorenza Rimassa, MD, Principal investigator, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04435977
- Sponsor's protocol ID
- ONC-2019-002
- Acronym
- Immunocabo
- Status last verified
- Jun 2020
- First submitted
- 12 Jun 2020
- Last updated
- 17 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Cabozantinib in Patients With Hepatocellular Carcinoma Progressing on or Intolerant to Prior Treatment With Immune Checkpoint Inhibitors: A Phase II Study (Immunocabo)
- ClinicalTrials.gov ID
- NCT04435977
- Acronym / sponsor ID
- Immunocabo / ONC-2019-002
- Conditions
- Hepatocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 30 Jan 2020 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Sep 2023 (estimated)
- First posted
- 17 Jun 2020 (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, single-center, Phase II trial designed to estimate in terms of PFS the efficacy of cabozantinib, given as second- or third- line treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 antibodies.
Detailed description
Subjects who meet all study eligibility criteria will take tablets containing 60 mg of cabozantinib once daily orally. Required dose reductions will be in decrements of 20 mg cabozantinib (maximum two dose reductions).
Subjects will receive study treatment as long as they continue to experience clinical benefit in the opinion of the investigator or until there is unacceptable toxicity.
Primary objective of this study is to evaluate the efficacy of cabozantinib, given as second- or third-line treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors.
Secondary objectives for this study are as follows:
- To evaluate the activity of cabozantinib, in terms of ORR (CR+PR) as per RECIST 1.1, duration of response, time to treatment failure (TTF), time to progression (TTP), and OS
- To evaluate the safety and tolerability of cabozantinib
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group assignement
| Arm | Type | Receives |
|---|---|---|
| Cabozantinib | Experimental | Drug: Cabozantinib 60 MGDrug: Cabozantinib Subjects who meet all study eligibility criteria will take tablets containing 60 mg of cabozantinib once daily orally. Required dose reductions will be in decrements of 20 mg cabozantinib (maximum two dose reductions). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted)
- A baseline tumor tissue (newly obtained) available at screening is optional. Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines and requirements for such procedure. Biopsy cannot be performed less than ten days before treatment start.
- The subject has disease that is not amenable to a locoregional treatment approach (eg, transplant, surgery, radiofrequency ablation, TACE)
- Patients must have documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic), the last of which includes immune checkpoint inhibitors. Alternatively, eligible patients may have experienced an immune-related, requiring treatment discontinuation.
- Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically not significant and/or stable on supportive therapy
Key exclusion criteria (30 listed)
- Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
- Child-Pugh score of B or C
- Any type of anticancer agent (including investigational) within 2 weeks before treatment start
- Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of treatment start. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy
- Prior cabozantinib treatment
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 |
|---|---|---|
| Cabozantinib 60 MG• The assigned dose for study treatment is 60 mg qd. Two dose reductions will be permitted (Table 2): * 60 mg qd to 40 mg qd (level 1) * 40 mg qd to 20 mg qd (level 2) | Drug | Cabozantinib |
Primary outcome
PFS
Time frame: through study completion, an average of 1 year
PFS on cabozantinib treatment (considering as PFS events: clinical or radiological progressive disease, per RECIST 1.1, or death).
2 secondary outcomes
ORR
Time frame: through study completion, an average of 1 year
safety and tolerability
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2020.
- 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.
Lorenza Rimassa, MD principal investigator
Istituto Clinico Humanitas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib 60 MG in people with Hepatocarcinoma, run by Istituto Clinico Humanitas at 1 site in Italy.
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 20 inclusion and 30 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 17 Jun 2020. 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 Italy. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lorenza Rimassa, MD (02 8224 ext. 4573, lorenza.rimassa@humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: through study completion, an average of 1 year). 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 17 Jun 2020.