Hepatocellular CarcinomaPhase 1NCT02988440
Study of Safety and Tolerability of PDR001 in Combination With Sorafenib and to Identify the Maximum Tolerated Dose and/or Phase 2 Dose for This Combination in Advanced Hepatocellular Patients
A Phase 1 study testing PDR001 and Sorafenib in people with Hepatocellular Carcinoma, run by Novartis Pharmaceuticals at 9 sites in 8 countries.
Trial summary
A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. There will be a dose escalation part and a dose expansion part. 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?
- PDR001 and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 9 sitesin 8 countries
- Study dates
- 20 Apr 2017to 27 Feb 2020
- 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
- Histologically or cytologically confirmed advanced (unresectable and/or metastatic) HCC
- Patients with advanced HCC not amenable for surgical or loco-regional treatment
- At least one measureable tumor lesion that that has not been previously locally
- Patients with current cirrhotic status of Child-Pugh class A only (5-6 points with total bilirubin < 2 mg/dL for dose-escalation) with no encephalopathy and no clinical ascites (ascites controlled by diuretics is also excluded in this study).
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patient must meet required laboratory values at the screening
- Normal electrocardiogram at screening
Who cannot join
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Invasion of the main portal vein and/or tumor involvement in more than 50% of the liver (applicable only for the dose-escalation part)
- Patients with Portal-caval shunts
- Prior or concomitant systemic anti-cancer treatment for advanced disease
- Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
- Cardiac or cardiac repolarization abnormality
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- Patients with active Hepatitis B infection (HBsAg positive) that are not receiving antiviral treatment are excluded
- Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)
- Loco-regional treatment within 4 weeks prior to initiation of study treatment.
Trial locations and contacts
9 sites in 8 countries.
9 sites in 8 countries
Japan2 sites
Novartis Investigative Site
Kashiwa, Chiba, 277 8577
Novartis Investigative Site
Yokohama, Kanagawa, 232 0024
About this study
Official title: A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. There will be a dose escalation part and a dose expansion part.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- PDR001, Sorafenib
- Keywords
- HCC, Hepatocellular carcinoma, Hepatocellular carcinoma (HCC), PDR001, liver cancer, immunotherapy liver, malignant hepatoma, Hepatocellular cancer, advanced hepatocellular carcinoma (HCC), advanced liver cancer, liver cancer progression, sorafenib, anti-PD1, first line
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Drug
PDR001 will be administered intravenously
SorafenibDrug
Sorafenib is formulated as a tablet.
| Study group | Role | What they receive |
|---|---|---|
| PDR001 + Sorafenib | Other | PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses) Receives: Drug: PDR001; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs
Measured: From baseline until 30 days of last dose of study treatment
Incidendence of Dose Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Measured: During the first 8 weeks of treatment
Dose interruptions
Tolerability measured by the number of subjects who have interruptions of study treatment
Measured: Until end of treatment, assessed for a median time of 4 months
Dose reductions
Tolerability measured by the number of subjects who have reductions of study treatment
Measured: Until end of treatment, assessed for a median time of 4 months
Dose intensity
Tolerability measured by the dose intensity of study treatment
Measured: Until end of treatment, assessed for a median time of 4 months
Secondary outcomes (6)
Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level
Overall response rate (ORR) as per the independent central radiology assessment will be summarized descriptively by dose level. The overall response rate (ORR) is defined as the proportion of patients with best overall response of CR or PR. The best overall response is the best response recorded using the independent central radiology review based on RECIST 1.1 from start of treatment until disease progression, death, start of new therapy, withdrawal of consent or cut-off date, whichever occurs first
Measured: Until end of treatment, assessed for a median time of 4 months
PDR001 trough concentration
Concentration of PDR001 in plasma
Measured: Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
Maximum concentration (Cmax) of sorafenib
The maximum (peak) observed plasma, drug concentration after single dose administration.
Measured: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Time to reach maximum concentration (Tmax) of sorafenib
The time to reach maximum (peak) plasma drug concentration after single dose administration (time)
Measured: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)
Area under the plasma concentration-time curve of sorafenib from time zero to time 't' where t is a defined time point after administration. t=8 hours (AUC0-8)
Measured: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib
Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady-state
Measured: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2016 (estimated)
- Study start20 Apr 2017
- Primary completion27 Feb 2020
- Study completion27 Feb 2020
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 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT02988440
- Sponsor's protocol ID
- CPDR001G2101
- Other IDs
- 2016-004131-20, 2016
- Status last verified
- Sep 2020
- First submitted
- 7 Dec 2016
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- 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 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT02988440
- Acronym / sponsor ID
- CPDR001G2101
- Conditions
- Hepatocellular Carcinoma
- Keywords
- HCC, Hepatocellular carcinoma, Hepatocellular carcinoma (HCC), PDR001, liver cancer, immunotherapy liver, malignant hepatoma, Hepatocellular cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2017 (actual)
- Primary completion
- 27 Feb 2020 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 9 Dec 2016 (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.
A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. There will be a dose escalation part and a dose expansion part.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PDR001 + Sorafenib | Other | Drug: PDR001, Drug: SorafenibPDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically or cytologically confirmed advanced (unresectable and/or metastatic) HCC
- Patients with advanced HCC not amenable for surgical or loco-regional treatment
- At least one measureable tumor lesion that that has not been previously locally
- Patients with current cirrhotic status of Child-Pugh class A only (5-6 points with total bilirubin < 2 mg/dL for dose-escalation) with no encephalopathy and no clinical ascites (ascites controlled by diuretics is also excluded in this study).
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Key exclusion criteria (9 listed)
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Invasion of the main portal vein and/or tumor involvement in more than 50% of the liver (applicable only for the dose-escalation part)
- Patients with Portal-caval shunts
- Prior or concomitant systemic anti-cancer treatment for advanced disease
- Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
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 |
|---|---|---|
| PDR001PDR001 will be administered intravenously | Drug | PDR001 + Sorafenib |
| SorafenibSorafenib is formulated as a tablet. | Drug | PDR001 + Sorafenib |
Primary outcome
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From baseline until 30 days of last dose of study treatment
Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs
Incidendence of Dose Limiting Toxicities (DLTs)
Time frame: During the first 8 weeks of treatment
A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Dose interruptions
Time frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the number of subjects who have interruptions of study treatment
Dose reductions
Time frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the number of subjects who have reductions of study treatment
Dose intensity
Time frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the dose intensity of study treatment
6 secondary outcomes
Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level
Time frame: Until end of treatment, assessed for a median time of 4 months
PDR001 trough concentration
Time frame: Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
Maximum concentration (Cmax) of sorafenib
Time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Time to reach maximum concentration (Tmax) of sorafenib
Time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)
Time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib
Time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for CPDR001G2101 from Novartis Clinical Trials WebsiteLink provided by the sponsor.
- 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
9 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PDR001 and Sorafenib in people with Hepatocellular Carcinoma, run by Novartis Pharmaceuticals at 9 sites in 8 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 7 inclusion and 9 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Japan, United States, Canada, Germany, Hong Kong and 3 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From baseline until 30 days of last dose of study treatment). The study lists 5 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 19 Dec 2020.