Advanced Hepatocellular CarcinomaPhase 2NCT01964235
Study of Efficacy and Safety INC280 in Patients With Advanced Hepatocellular Carcinoma
A Phase 2 study testing INC280 in people with Advanced Hepatocellular Carcinoma, run by Novartis Pharmaceuticals at 15 sites in 7 countries.
Trial summary
This study is establish whether INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway and whose disease progressed while on, or after, treatment with sorafenib or who are intolerant to sorafenib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- INC280
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 15 sitesin 7 countries
- Study dates
- Dec 2016to Jul 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed c-MET pathway dysregulation.- Hepatocellular carcinoma stage B or C according to the Barcelona Clinic Liver cancer staging classification. - Current cirrhotic status of Child-Pugh class A with no encephalopathy. - Documented disease progression during or after discontinuation of sorafenib treatment or intolerance to sorafenib treatment. - Measurable disease as determined by RECIST v1.1. - ECOG performance status ≤ 1
Who cannot join
- Previous local antineoplastic therapy or investigational drug completed less than 5 half-lives of the agent prior to randomization and have not recovered from clinically significant toxicity from such treatment to grade ≤1 by the NCI-CTCAE. - Received any targeted therapy other than sorafenib.
- Active bleeding within 28 days prior to screening visit including variceal bleeding (esophageal varices should be treated according to standard practice and procedure completed 28 days prior to screening visit). - Clinically significant venous or arterial thrombotic disease within past 6 months.
Trial locations and contacts
15 sites in 7 countries.
15 sites in 7 countries
France4 sites
Novartis Investigative Site
Clichy, 92110
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Montpellier, 34298
Novartis Investigative Site
Nice, 06202
United States2 sites
Massachusetts General Hospital Mass General Hospital
Boston, Massachusetts, 02115
Research Medical Center Onc Dept
Kansas City, Missouri, 64132
Australia2 sites
Novartis Investigative Site
Heidelberg, Victoria, 3084
Novartis Investigative Site
Kogarah, New South Wales, 2217
Germany2 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Würzburg, 97080
Hong Kong2 sites
Novartis Investigative Site
Hong Kong
Novartis Investigative Site
Hong Kong SAR
Switzerland2 sites
Novartis Investigative Site
Bern, 3010
Novartis Investigative Site
Geneva, 1211
About this study
Official title: A Randomized Phase II, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of INC280 in Adult Patients With Advanced Hepatocellular Carcinoma After Progression or Intolerance to Sorafenib Treatment
This study is establish whether INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway and whose disease progressed while on, or after, treatment with sorafenib or who are intolerant to sorafenib.
Patients will be randomized in a 2:1 ratio to receive INC280 at 600mg BID plus best supportive care (BSC) or placebo plus BSC, until disease progression or intolerable to study treatment. Patients treated with placebo plus BSC will have the opportunity to receive INC280 treatment upon documented further disease progression (RECIST 1.1) per investigator's discretion after unblinding.
Patient will be stratified to geographical region (Asia vs Rest of World ) and tumor burden (present macroscopic vascular invasion and/or extra-hepatic spread vs not present).
Read the detailed description
Study was cancelled by Sponsor prior to enrollment of patients.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- INC280, Placebo
- Keywords
- INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INC280Drug
INC280 will be administered orally and continuously on a twice a day dosing schedule.
PlaceboDrug
Placebo will be administered orally and continuously on a twice a day dosing schedule.
| Study group | Role | What they receive |
|---|---|---|
| INC280 plus best supportive care | Experimental | Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care. Receives: Drug: INC280 |
| Placebo plus best supportive care | Placebo comparator | Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression.
Measured: baseline, 6 weeks up to 6 months
Secondary outcomes (8)
Best Overall Response
Best overall response is defined as the best response recorded from the date of randomization until the date of last tumor assessment per RECIST version 1.1.
Measured: date of treatment, every 6 weeks up to 6 months
Overall Response Rate
Overall Response Rate is defined as the proportion of patients with a best overall response of complete response or partial response at any time on study per RECIST version 1.1.
Measured: baseline, every 6 weeks up to 6 months
Disease Control Rate
Disease control rate is defined as the proportion of patients with a best overall response of complete response, partial response or stable disease at any time on study per RECIST version 1.1.
Measured: baseline, every 6 weeks up to 6 months
Progression Free Survival
Progression free survival is defined as the time from date of randomization to the date of the first radiologically documented progression or death due to any cause. If a patient has not experienced radiologically documented progression or death, progression free survival is censored at the date of last adequate tumor assessment.
Measured: randomization, every 6 weeks up to 6 months
Overall Survival
Overall survival is defined as the time from date of randomization to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
Measured: randomization until death, average 10 months
Safety: adverse events, serious adverse events
Frequency, duration and severity of adverse events.
Measured: From baseline until 30 days post study treatment
Safety: hematology and chemistry values, vital signs, electrocardiograms
Change from baseline values.
Measured: From baseline until end of treatment, average 6 months from baseline
Tolerability of study drug
Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.
Measured: From date of randomization until end of treatment, average 6 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2013 (estimated)
- Study startDec 2016
- Primary completionJul 2019 (estimated)
- Study completionJul 2019 (estimated)
Why it stopped: Study was cancelled by Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01964235
- Sponsor's protocol ID
- CINC280X2203
- Status last verified
- Aug 2016
- First submitted
- 14 Oct 2013
- Last updated
- 1 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of INC280 in Adult Patients With Advanced Hepatocellular Carcinoma After Progression or Intolerance to Sorafenib Treatment
- ClinicalTrials.gov ID
- NCT01964235
- Acronym / sponsor ID
- CINC280X2203
- Conditions
- Advanced Hepatocellular Carcinoma
- Keywords
- INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was cancelled by Sponsor.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2016
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 17 Oct 2013 (estimated)
- 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 study is establish whether INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway and whose disease progressed while on, or after, treatment with sorafenib or who are intolerant to sorafenib.
Patients will be randomized in a 2:1 ratio to receive INC280 at 600mg BID plus best supportive care (BSC) or placebo plus BSC, until disease progression or intolerable to study treatment. Patients treated with placebo plus BSC will have the opportunity to receive INC280 treatment upon documented further disease progression (RECIST 1.1) per investigator's discretion after unblinding.
Patient will be stratified to geographical region (Asia vs Rest of World ) and tumor burden (present macroscopic vascular invasion and/or extra-hepatic spread vs not present).
Detailed description
Study was cancelled by Sponsor prior to enrollment of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INC280 plus best supportive care | Experimental | Drug: INC280Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care. |
| Placebo plus best supportive care | Placebo comparator | Drug: PlaceboApproximately 23 patients will be treated with matching placebo twice a day plus best supportive care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Confirmed c-MET pathway dysregulation.- Hepatocellular carcinoma stage B or C according to the Barcelona Clinic Liver cancer staging classification. - Current cirrhotic status of Child-Pugh class A with no encephalopathy. - Documented disease progression during or after discontinuation of sorafenib treatment or intolerance to sorafenib treatment. - Measurable disease as determined by RECIST v1.1. - ECOG performance status ≤ 1
Key exclusion criteria (2 listed)
- Previous local antineoplastic therapy or investigational drug completed less than 5 half-lives of the agent prior to randomization and have not recovered from clinically significant toxicity from such treatment to grade ≤1 by the NCI-CTCAE. - Received any targeted therapy other than sorafenib.
- Active bleeding within 28 days prior to screening visit including variceal bleeding (esophageal varices should be treated according to standard practice and procedure completed 28 days prior to screening visit). - Clinically significant venous or arterial thrombotic disease within past 6 months.
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 |
|---|---|---|
| INC280INC280 will be administered orally and continuously on a twice a day dosing schedule. | Drug | INC280 plus best supportive care |
| PlaceboPlacebo will be administered orally and continuously on a twice a day dosing schedule. | Drug | Placebo plus best supportive care |
Primary outcome
Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Time frame: baseline, 6 weeks up to 6 months
Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression.
8 secondary outcomes
Best Overall Response
Time frame: date of treatment, every 6 weeks up to 6 months
Overall Response Rate
Time frame: baseline, every 6 weeks up to 6 months
Disease Control Rate
Time frame: baseline, every 6 weeks up to 6 months
Progression Free Survival
Time frame: randomization, every 6 weeks up to 6 months
Overall Survival
Time frame: randomization until death, average 10 months
Safety: adverse events, serious adverse events
Time frame: From baseline until 30 days post study treatment
Safety: hematology and chemistry values, vital signs, electrocardiograms
Time frame: From baseline until end of treatment, average 6 months from baseline
Tolerability of study drug
Time frame: From date of randomization until end of treatment, average 6 months from baseline
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing INC280 in people with Advanced Hepatocellular Carcinoma, run by Novartis Pharmaceuticals at 15 sites in 7 countries.
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 1 inclusion and 2 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 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France, United States, Australia, Germany, Hong Kong and 2 more countries. 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. Some participants in this study may receive a placebo. 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?
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?
Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (time frame: baseline, 6 weeks up to 6 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 1 Sep 2016.