Hepatocellular CarcinomaPhase 2NCT03109886
Study of Milciclib in Patients With Unresectable/Metastatic Hepatocellular Carcinoma
A Phase 2 study testing Milciclib maleate in people with Hepatocellular Carcinoma, run by Tiziana Life Sciences LTD at 14 sites in 3 countries.
Trial summary
The primary aim of this exploratory study is to test the safety and tolerability of milciclib when administered orally at 100 mg in patients with recurrent or metastatic Hepatocellular Carcinoma. The evaluation of the efficacy profile is a secondary objective of the study. 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?
- Milciclib maleate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 12 Jul 2017to 20 Jun 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
- Patients with diagnosis of HCC, confirmed by histology or radiology according to American Association for the Study of Liver Diseases/European Association for the Study of the Liver (AASLD/EASL) criteria prior to the start of the investigational product. Imaging characteristics should be retrieved from at least a 3-phase liver protocol CT or MRI with target tumor lesion(s) demonstrating arterial hyper-enhancement and wash-out in the venous phase;
- Tumor stages eligible for the study are defined as:
- HCC within the Barcelona Clinic Liver Cancer (BCLC) stage C. In case of portal vein thrombosis (PVT) an associated target lesion in the liver parenchyma should be clearly defined. PVT without associated target lesion are not eligible to the study;
- Untreatable post-chemoembolization (TACE) or post-radioembolization (TARE) progression defined as BCLC stage B or C with radiographic progression according to mRECIST after TACE or TARE not eligible for further surgical or loco-regional therapy;
- Recurring HCC non eligible for pre-transplant downstaging protocols or for resection;
- Patients must have failed sorafenib treatment or be intolerant to sorafenib or actively refusing sorafenib
Show all 13Show fewer
- Failing sorafenib treatment is defined if after ≥ 14 days of therapy (not necessarily consecutive) radiology progression is ascertained according to mRECIST;
- Intolerant to sorafenib treatment is defined as a sorafenib related Grade 2 or greater adverse event (CTC-AE) that continues or recurs after sorafenib treatment interruption for 7 days or dose reduction;
- Active refusal should be documented by a written and signed patient declaration to be filed in the clinical records;
- Child-Pugh score ≤ 6 (class A);
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radioembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ≥4 weeks prior to study entry with documentation of progressive or recurrent disease;
- Signed and dated Investigational Review Board/Independent Ethics Committee (IRB/IEC) approved Informed Consent/Genetic Consent.
Who cannot join
- Prior use of any systemic anti-cancer therapy (including experimental agents and immunotherapy) except for sorafenib and second line treatment with regorafenib discontinued for intolerance within 14 days;
- Known fibrolamellar HCC or mixed hepato-cholangiocarcinoma;
- Grade 3 oesophageal varices, regardless of previous bleeding episodes on endoscopy performed no more than in the last 12 months;
- Clinical meaningful ascites defined as CTCAE Grade≥2. Patient who have been on a stable medication regimen for at least 2 months to manage ascites are eligible if they show no ascites at the clinical examination. Patients with clinically undetectable ascites who are Child A with detectable ascites at CT/MRI are eligible to the protocol;
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
Italy6 sites
AOU S. Orsola Malpighi Bologna
Bologna, 40138
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, 20122
Azienda Ospedaliera Universitaria Policlinico di Modena
Modena, 41124
A.O.U. Federico II
Naples, 80131
A.O. U. Policlinico Paolo Giaccone
Palermo, 90127
Istituto Clinico Humanitas
Rozzano, MI, 20089
Greece4 sites
Ippokrateio General Hospital of Athens
Athens, 11527
Laiko General Hospital of Athens
Athens, 11527
General University Hospital of Larissa
Larissa, 41110
University General Hospital of Thessaloniki - AHEPA
Thessaloniki, 54636
Israel4 sites
Rambam Health Corporation
Haifa, 31096
Rabin Medical Center - Beilinson Hospital
Petah Tikva, 4941492
The Sheba Academic Medical Center Hospital - Tel Hashomer
Ramat Gan
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
About this study
Official title: Phase IIA Exploratory Study of Oral Milciclib Maleate in Patients With Unresectable or Metastatic Hepatocellular Carcinoma
The primary aim of this exploratory study is to test the safety and tolerability of milciclib when administered orally at 100 mg in patients with recurrent or metastatic Hepatocellular Carcinoma. The evaluation of the efficacy profile is a secondary objective of the study. Moreover, markers expression in tumor cells and plasma will be studied and described in association with the clinical outcome.
Eligible patients will receive milciclib orally on a daily schedule for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) unless patient refusal, consent withdrawal, Investigator's decision, unacceptable toxicity or death whichever occurs earlier.
Read more
At the end of Cycle 3, treatment will be stopped, and based on the results of the tumor assessment performed on Day 90 (±3 days) from treatment start, patients will be followed as here below detailed:
- patients with Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) will be followed for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier) and will be assessed for efficacy in the follow-up period up to Day 180 from treatment start;
- patients with progressive disease will be followed only for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier).
After the completion of three cycles, patients who, in the Investigator's judgment, are benefiting from treatment with milciclib, will resume treatment and will remain on study up to Day 180 from treatment start, unless withdrawal criteria are met earlier.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Milciclib maleate
- Keywords
- Unresectable Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma, Child-Pugh Class A
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milciclib maleateDrug
Also called PHA-848125AC
100 mg/day once daily, for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) unless patient refusal, consent withdrawal, Investigator's decision, unacceptable toxicity or death whichever occurs earlier. After the completion of three cycles, patients who, in the Investigator's judgment, are benefiting from treatment with milciclib, will resume treatment and will remain on study up to Day 180 from treatment start, unless withdrawal criteria are met earlier.
| Study group | Role | What they receive |
|---|---|---|
| Milciclib maleate | Experimental | milciclib maleate ,10, 50 and 100 mg hard gelatine capsules , 100 mg once daily, for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) Receives: Drug: Milciclib maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Safety Profile
Overall safety profile, evaluated on the basis of laboratory (i.e. hematology and blood chemistry, urinalysis, vital signs, ophthalmologic examinations) and adverse events emerging during the trial, will be determined. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 will be used for the severity grading of adverse events and of hematological and blood chemistry abnormalities
Measured: From Informed Consent signature to 30 days after last dose intake up to Day 180 from treatment start
Secondary outcomes (6)
Objective Response Rate (ORR)
Confirmed CR. The objective tumor assessment will be made according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST) criteria for Hepatocellular Carcinoma (HCC). Conventional RECIST 1.1 will be also assessed. ORR will be assessed locally and confirmed by an Independent Central Review.
Measured: At screening; During treatment at Day 45 and 90; During follow up at Day 180 for patients not progressed at previous assessments
Objective Response Rate (ORR)
Confirmed PR. The objective tumor assessment will be made according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST) criteria for Hepatocellular Carcinoma (HCC). Conventional RECIST 1.1 will be also assessed. ORR will be assessed locally and confirmed by an Independent Central Review.
Measured: At screening; During treatment at Day 45 and 90; During follow up at Day 180 for patients not progressed at previous assessments
Progression-Free Survival (PFS)
PFS is evaluated since study treatment start to progression, based on mRECIST tumor assessment, or death for any causes.
Measured: From treatment start to date of progression assessed on Day 45, 90 or 180 or to date of death if before day 180
Time to Progression (TPP)
TPP is evaluated since study treatment start to progression, based on mRECIST tumor assessment or death due to disease progression in the absence of previous documented Progression Disease (PD).
Measured: From treatment start to date of progression assessed on Day 45, 90 or 180 or to date of death if before day 180
TPP-3 months
Proportion of evaluable patients known to be alive and progression free based on mRECIST tumor assessment at ≥ 3 months since study treatment start out of the total number of evaluable patients (TTP-3 months)
Measured: Based on tumor assessment at or after 3 months from treatment start
Duration of overall Response (DoR)
DoR is measured from the time measurement criteria are first met for CR/PR based on mRECIST tumor assessment, until the first date that recurrence or PD is objectively documented or death date due to tumor progression in the absence of previous documented PD.
Measured: Based on assessments performed on Day 45, 90 or 180 or date of death if before day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2017
- Study start12 Jul 2017
- Primary completion16 May 2019
- Study completion20 Jun 2019
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.
- 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
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tiziana Life Sciences LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fayez M Hamzeh, MD, Study chair, Tiziana Life Sciences LTDAngelo Sangiovanni, MD, PHD, Principal investigator, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Milano, ItalyArmando Santoro, MD, Principal investigator, Istituto Clinico Humanitas - Rozzano (MI), Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03109886
- Sponsor's protocol ID
- CDKO-125a-010
- Other IDs
- 2017-000144-18, 2017
- Status last verified
- Oct 2021
- First submitted
- 30 Mar 2017
- Last updated
- 12 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIA Exploratory Study of Oral Milciclib Maleate in Patients With Unresectable or Metastatic Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03109886
- Acronym / sponsor ID
- CDKO-125a-010
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Unresectable Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma, Child-Pugh Class A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Tiziana Life Sciences LTDIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2017 (actual)
- Primary completion
- 16 May 2019 (actual)
- Study completion
- 20 Jun 2019 (actual)
- First posted
- 12 Apr 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.
The primary aim of this exploratory study is to test the safety and tolerability of milciclib when administered orally at 100 mg in patients with recurrent or metastatic Hepatocellular Carcinoma. The evaluation of the efficacy profile is a secondary objective of the study. Moreover, markers expression in tumor cells and plasma will be studied and described in association with the clinical outcome.
Eligible patients will receive milciclib orally on a daily schedule for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) unless patient refusal, consent withdrawal, Investigator's decision, unacceptable toxicity or death whichever occurs earlier.
At the end of Cycle 3, treatment will be stopped, and based on the results of the tumor assessment performed on Day 90 (±3 days) from treatment start, patients will be followed as here below detailed:
- patients with Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) will be followed for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier) and will be assessed for efficacy in the follow-up period up to Day 180 from treatment start;
- patients with progressive disease will be followed only for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier).
After the completion of three cycles, patients who, in the Investigator's judgment, are benefiting from treatment with milciclib, will resume treatment and will remain on study up to Day 180 from treatment start, unless withdrawal criteria are met earlier.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Milciclib maleate | Experimental | Drug: Milciclib maleatemilciclib maleate ,10, 50 and 100 mg hard gelatine capsules , 100 mg once daily, for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with diagnosis of HCC, confirmed by histology or radiology according to American Association for the Study of Liver Diseases/European Association for the Study of the Liver (AASLD/EASL) criteria prior to the start of the investigational product. Imaging characteristics should be retrieved from at least a 3-phase liver protocol CT or MRI with target tumor lesion(s) demonstrating arterial hyper-enhancement and wash-out in the venous phase;
- Tumor stages eligible for the study are defined as:
- Patients must have failed sorafenib treatment or be intolerant to sorafenib or actively refusing sorafenib
- Child-Pugh score ≤ 6 (class A);
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
Key exclusion criteria (4 listed)
- Prior use of any systemic anti-cancer therapy (including experimental agents and immunotherapy) except for sorafenib and second line treatment with regorafenib discontinued for intolerance within 14 days;
- Known fibrolamellar HCC or mixed hepato-cholangiocarcinoma;
- Grade 3 oesophageal varices, regardless of previous bleeding episodes on endoscopy performed no more than in the last 12 months;
- Clinical meaningful ascites defined as CTCAE Grade≥2. Patient who have been on a stable medication regimen for at least 2 months to manage ascites are eligible if they show no ascites at the clinical examination. Patients with clinically undetectable ascites who are Child A with detectable ascites at CT/MRI are eligible to the protocol;
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 |
|---|---|---|
| Milciclib maleateAlso: PHA-848125AC100 mg/day once daily, for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) unless patient refusal, consent withdrawal, Investigator's decision, unacceptable toxicity or death whichever occurs earlier. After the completion of three cycles, patients who, in the Investigator's judgment, are benefiting from treatment with milciclib, will resume treatment and will remain on study up to Day 180 from treatment start, unless withdrawal criteria are met earlier. | Drug | Milciclib maleate |
Primary outcome
Overall Safety Profile
Time frame: From Informed Consent signature to 30 days after last dose intake up to Day 180 from treatment start
Overall safety profile, evaluated on the basis of laboratory (i.e. hematology and blood chemistry, urinalysis, vital signs, ophthalmologic examinations) and adverse events emerging during the trial, will be determined. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 will be used for the severity grading of adverse events and of hematological and blood chemistry abnormalities
6 secondary outcomes
Objective Response Rate (ORR)
Time frame: At screening; During treatment at Day 45 and 90; During follow up at Day 180 for patients not progressed at previous assessments
Objective Response Rate (ORR)
Time frame: At screening; During treatment at Day 45 and 90; During follow up at Day 180 for patients not progressed at previous assessments
Progression-Free Survival (PFS)
Time frame: From treatment start to date of progression assessed on Day 45, 90 or 180 or to date of death if before day 180
Time to Progression (TPP)
Time frame: From treatment start to date of progression assessed on Day 45, 90 or 180 or to date of death if before day 180
TPP-3 months
Time frame: Based on tumor assessment at or after 3 months from treatment start
Duration of overall Response (DoR)
Time frame: Based on assessments performed on Day 45, 90 or 180 or date of death if before day 180
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 12 Oct 2021.
- 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.
Fayez M Hamzeh, MD study chair
Tiziana Life Sciences LTD
Angelo Sangiovanni, MD, PHD principal investigator
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Milano, Italy
Armando Santoro, MD principal investigator
Istituto Clinico Humanitas - Rozzano (MI), Italy
14 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Milciclib maleate in people with Hepatocellular Carcinoma, run by Tiziana Life Sciences LTD at 14 sites in 3 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 13 inclusion and 4 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 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Italy, Greece, Israel. 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?
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?
Overall Safety Profile (time frame: From Informed Consent signature to 30 days after last dose intake up to Day 180 from treatment start). 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 Oct 2021.