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Trial record 4 of 4 for:    PHA-848125AC

Study of Milciclib in Patients With Unresectable/Metastatic Hepatocellular Carcinoma

This study is currently recruiting participants.
Verified October 2017 by Tiziana Life Sciences, PLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT03109886
First Posted: April 12, 2017
Last Update Posted: October 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Tiziana Life Sciences, PLC
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma Drug: Milciclib maleate Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IIA Exploratory Study of Oral Milciclib Maleate in Patients With Unresectable or Metastatic Hepatocellular Carcinoma

Further study details as provided by Tiziana Life Sciences, PLC:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]
    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.

  • 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 ]
    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.

  • 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 ]
    PFS is evaluated since study treatment start to progression, based on mRECIST tumor assessment, or death for any causes.

  • 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 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).

  • TPP-3 months [ Time Frame: Based on tumor assessment at or after 3 months from treatment start ]
    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)

  • 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 ]
    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.


Estimated Enrollment: 30
Actual Study Start Date: July 12, 2017
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Milciclib maleate
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)
Drug: Milciclib maleate
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.
Other Name: PHA-848125AC

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. 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;
    2. 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;
    3. 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

    1. Failing sorafenib treatment is defined if after ≥ 14 days of therapy (not necessarily consecutive) radiology progression is ascertained according to mRECIST;
    2. 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;
    3. 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.

Exclusion Criteria:

  • 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;
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03109886


Contacts
Contact: Betty Liong Chu +1 646 396 4078 BChu@tizianalifesciences.com
Contact: Monica Miani +39 3480840579 monica.miani@clioss.com

Locations
Greece
Ippokrateio General Hospital of Athens Not yet recruiting
Athens, Greece, 11527
Contact: Spiros Dourakis, MD       academic@hippocratio.gr   
Contact    0030 213 2088129      
Principal Investigator: Spiros Dourakis, MD         
Laiko General Hospital of Athens Recruiting
Athens, Greece, 11527
Contact: George Papatheodoridis, MD       gepapath@med.uoa.gr   
Principal Investigator: George Papatheodoridis, MD         
General University Hospital of Larissa Recruiting
Larissa, Greece, 41110
Contact: George Dalekos, MD       dalekos@med.uth.gr   
Principal Investigator: George Dalekos, MD         
University General Hospital of Thessaloniki - AHEPA Not yet recruiting
Thessaloniki, Greece, 54636
Contact: Georgios Germanidis, MD       geogerm@auth.gr   
Principal Investigator: Georgios Germanidis, MD         
Israel
Rambam Health Corporation Recruiting
Haifa, Israel, 31096
Contact: Ella Veitsman, MD       e_veitsman@rambam.health.gov.il   
Principal Investigator: Ella Veitsman, MD         
Rabin Medical Center - Beilinson Hospital Recruiting
Petah Tikva, Israel, 4941492
Contact: Salomon Stemmer, MD       shtemers@clalit.org.il   
Principal Investigator: Salomon Stemmer         
The Sheba Academic Medical Center Hospital - Tel Hashomer Recruiting
Ramat Gan, Israel
Contact: Ziv Ben Ari, MD       ziv.ben-ari@sheba.health.gov.il   
Principal Investigator: Ziv Ben Ari, MD         
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Contact: Ravit Geva, MD         
Contact    972-3-6973984      
Principal Investigator: Ravit Geva, MD         
Italy
Istituto Clinico Humanitas Recruiting
Rozzano, MI, Italy, 20089
Contact: Armando Santoro, MD    +39-02-8224 4080    armando.santoro@cancercenter.humanitas.it   
Principal Investigator: Armando Santoro, MD         
AOU S. Orsola Malpighi Bologna Recruiting
Bologna, Italy, 40138
Contact: Fabio Piscaglia, MD    +39 0512142260    fabio.piscaglia@unibo.it   
Principal Investigator: Fabio Piscaglia, MD         
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Recruiting
Milano, Italy, 20122
Contact: Angelo Sangiovanni, MD    +39 0255035427    angelo.sangiovanni@unimi.it   
Principal Investigator: Angelo Sangiovanni, MD         
A.O. U. Policlinico Paolo Giaccone Recruiting
Palermo, Italy, 90127
Contact: Calogero Cammà, MD    +39 0916552280    calogero.camma@unipa.it   
Principal Investigator: Calogero Cammà, MD         
Turkey
Ege Üniversitesi Tıp Fakültesi - Gastroenteroloji Bilim Dalı Not yet recruiting
İzmir, Bornova/İzmir, Turkey, 35040
Contact: Ulus Salih Akarca, MD         
Principal Investigator: Ulus Salih Akarca, MD         
Ankara Üniversitesi Tıp Fakültesi - Cebeci Hastanesi Gastroenteroloji Kliniği Not yet recruiting
Ankara, Cebeci-Ankara, Turkey, 06100
Contact: Ramazan Idilman, MD       Ramazan.Idilman@medicine.ankara.edu.tr   
Principal Investigator: Ramazan Idilman, MD         
Sponsors and Collaborators
Tiziana Life Sciences, PLC
Investigators
Study Chair: Yaron Ilan, MD Tiziana Life Sciences, PLC
Principal Investigator: Angelo Sangiovanni, MD Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Milano, Italy
Principal Investigator: Armando Santoro, MD Istituto Clinico Humanitas - Rozzano (MI), Italy
  More Information

Responsible Party: Tiziana Life Sciences, PLC
ClinicalTrials.gov Identifier: NCT03109886     History of Changes
Other Study ID Numbers: CDKO-125a-010
2017-000144-18 ( EudraCT Number )
First Submitted: March 30, 2017
First Posted: April 12, 2017
Last Update Posted: October 11, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Tiziana Life Sciences, PLC:
Unresectable Hepatocellular Carcinoma
Metastatic Hepatocellular Carcinoma
Child-Pugh Class A

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action