Study of Milciclib in Patients With Unresectable/Metastatic Hepatocellular Carcinoma

• Register: ClinicalTrials.gov
• Last refreshed on: 26 October 2021
• Main ID: NCT03109886
• Date of registration: 30/03/2017
• Prospective Registration: Yes
• Primary sponsor: Tiziana Life Sciences, PLC
• Public title: Study of Milciclib in Patients With Unresectable/Metastatic Hepatocellular Carcinoma
• Scientific title: Phase IIA Exploratory Study of Oral Milciclib Maleate in Patients With Unresectable or Metastatic Hepatocellular Carcinoma
• Date of first enrolment: July 12, 2017
• Target sample size: 31
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03109886
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Greece, Israel, Italy, Turkey

Contacts

• Name: Fayez M Hamzeh, MD
• Affiliation: Tiziana Life Sciences, PLC

• Name: Armando Santoro, MD
• Affiliation: Istituto Clinico Humanitas - Rozzano (MI), Italy

• Name: Angelo Sangiovanni, MD, PHD
• Affiliation: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Milano, Italy

Key inclusion & exclusion 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;



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hepatocellular Carcinoma

Intervention(s)

Drug: Milciclib maleate

Primary Outcome(s)

Overall Safety Profile [Time Frame: From Informed Consent signature to 30 days after last dose intake up to Day 180 from treatment start]

Secondary Outcome(s)

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]

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]

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]

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]

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

Secondary ID(s)

2017-000144-18

CDKO-125a-010

Source(s) of Monetary Support

Please refer to primary and secondary sponsors