Trial Title:
Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC
NCT ID:
NCT05546879
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Atezolizumab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Multicentric prospective single arm phase 1b trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NP137
Description:
NP137 at 9 or 14 mg/kg IV will be administered every 21 days.
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of
each 21-days cycle
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each
21-day cycle
Arm group label:
Experimental
Summary:
The study will assess the safety of the association of NP137 with the standard of care
Atezolizumab-Bevacizumab in first line setting in patients with unresectable
hepatocellular carcinoma.The study drug which is tested is the NP137 in association with
Atezolizumab-Bevacizumab to allow a better tumor response as well as better survival
outcomes with an acceptable safety.
Detailed description:
The study is a multicentric, prospective, single arm phase 1b trial. This study will
enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion
Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on
a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended
dose of NP137 .The Expansion Phase will start after completion of Safety Lead-in Phase at
the confirmed dose and will include 40 patients. Patients will be assigned to the
experimental single arm (NP137+ Atezolizumab-Bevacizumab).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males or females ≥ 18 years of age
2. Histologically confirmed (liver biopsy within 24 previous weeks) and documented
unresectable hepatocellular carcinoma
3. Patients with a BCLC C or BCLC B status ineligible for or in failure of locoregional
treatment, as per the Barcelona Clinic Liver Cancer (BCLC) staging system
4. No prior systemic therapy for advanced HCC
5. Liver tumor burden < 50% of the liver (per Investigator judgment)
6. Child-Pugh A (≤ 6) without any history of cirrhotic decompensation within the past 6
months
7. Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen
positive)
8. Willing to have liver biopsy between C4 and C5
9. Presence of a measurable tumor per RECIST v1.1 criteria
10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
11. Life expectancy ≥ 12 weeks
12. Absence of previous liver decompensation
13. In case of cirrhosis, last esophageal varices detection by esogastroduodenal
endoscopy have to be performed within last the 6 months before inclusion
14. Adequate hematologic function prior to the first dose of NP137, defined as:
Absolute neutrophils count ≥ 1500 cells/μL 14.2. Hemoglobin ≥ 9 g/dL with no
transfusion within 4 weeks prior to first planned dose of NP137 14.3. Platelet count
> 50,000/μL with no transfusion within 2 weeks prior to first planned dose of
NP137
15. Adequate renal function prior to first dose, defined as:
15.1. Serum creatinine < 1.5 × Upper limit of normal (ULN ) 15.2. Creatinine
clearance ≥ 30 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine
≥ 1.5 × ULN
16. Adequate hepatic function prior first dose, defined as AST/ALT ≤ 5 × ULN
17. Women patients of childbearing potential must have a negative serum pregnancy test
at screening and baseline, and be willing to use a highly effective contraception.
The patient should be advised to continue the contraception for at least 6 months
following the completion of dosing. Women with cessation for > 24 months of
previously occurring menses, or women of any age who have had a hysterectomy, or
have had both ovaries removed will be considered to be of non-childbearing
potential.
18. Male patients of reproductive potential must be willing to use one acceptable method
of contraception, as judged by Investigator and Sponsor and/or to refrain from
donating sperm from the time of screening through at least 6 months following the
completion of dose administration.
19. Amenable to computed tomography (CT) with 3 or 4 phase liver or magnetic resonance
imaging (MRI) of abdomen and pelvis, and CT of chest, or MRI of whole body, for
initial tumor size measurements and subsequent follow-up.
20. Absence of other clinically relevant abnormalities for any screening laboratory test
results as judged by the Investigator and Sponsor.
21. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures.
22. Able to understand and provide written informed consent
23. Patients covered by Health Insurance System
Exclusion Criteria:
1. Any known history of encephalopathy within 6 months prior to first planned dose of
treatment
2. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
high-risk for bleeding
3. Known esophageal varices with recent history of bleeding (within previous 6 months)
4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures
5. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
6. Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to
first planned dose of treatment.
7. Major surgical procedures, open biopsy or significant traumatic injury ≤ 4 weeks
prior to first dose of treatment or anticipation of major surgical procedure during
the course of the trial, minor surgical procedures ≤ 1 week of first planned dose
(the surgical wound must be fully healed)
8. Local therapy to liver within 28 days prior to initiation of study treatment or
non-recovery from side effects of any such procedure
9. Any clinically significant cardiovascular condition as judged by the Investigator
(such as New York Heart Association Class II or greater cardiac failure, myocardial
infarction, or cerebrovascular accident within 3 months prior to Day 1 of Cycle 1,
uncontrolled arterial hypertension, unstable arrhythmia, or unstable angina)
10. Severe or uncontrolled renal condition
11. Untreated chronic hepatitis B
12. Co-infection of HBV and HCV
13. Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1
visit
14. Contraindication to additionnal liver biopsy planned between C4 and C5
15. Contraindication to iodinated contrast agent infusion
16. Known current alcohol (> 20g/ Day in women and > 30g/ Day in men) or
substance abuse
17. History of leptomeningeal disease
18. Active or history of autoimmune disease or immune deficiency
19. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on
screening chest computed tomography scan
20. Known active tuberculosis
21. History of malignancy other than HCC within 5 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death
22. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
or within at least 6 months after the last dose of treatment
23. Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases
24. Uncontrolled tumor-related pain
25. Uncontrolled or symptomatic hypercalcemia
26. Treatment with systemic immunostimulatory agents
27. Inadequately controlled arterial hypertension
28. Prior history of hypertensive crisis or hypertensive encephalopathy
29. Evidence of bleeding diathesis or significant coagulopathy
30. History of intestinal obstruction and/or clinical signs or symptoms of GI
obstruction including sub-occlusive disease related to the underlying disease or
requirement for routine parenteral hydration
31. Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
32. Metastatic disease that involves major airways or blood vessels, or centrally
located mediastinal tumor masses
33. Known clinically significant or life threatening organ or systemic disease such that
in the opinion of the Investigator, the significance of the disease will compromise
the patient's participation in the trial
34. Known intolerance or hypersensitivity to the active ingredient or to one of the
components of the study drug
35. Persistent toxicities related to prior treatment of grade greater than 1
36. Subjects with active infection
37. History of bone marrow allograft or solid organ transplant
38. Subjects requiring corticosteroid therapy at a dose equivalent to more than 10 mg of
prednisone equivalent dose per day (corticosteroid administration is permitted by a
route resulting in minimal systemic exposure [cutaneous, rectal, articular, ocular
or inhalation] is authorized).
39. Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant
human or humanised antibodies
40. History of gastrointestinal perforations and fistulae
41. Uncontrolled or symptomatic proteinuria
42. Active aneurysm considered as unstable and/or at high risk of complication
43. Patients who experienced immune-mediated pericardial disorders during previous
treatment by immune checkpoint blockade therapies, including anti-CTLA4, anti-PD1,
and anti-PDL1 therapeutic antibodies
44. Subject who participate or plan to participate in another interventional clinical
trial or who is in exclusion period for another study,
45. Subject who cannot be contacted in case of emergency
46. Persons referred to in Articles L1121-5 to L1121-8 of the French code of public
health (this corresponds to all persons protected: pregnant or parturient women,
breastfeeding mothers, persons deprived of liberty by judicial or administrative
decision, persons subject to a legal protection measure).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU de GRENOBLE ALPES
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Recruiting
Contact:
Last name:
ROTH, Gaël
Phone:
GRoth@chu-grenoble.fr
Start date:
March 15, 2023
Completion date:
March 15, 2027
Lead sponsor:
Agency:
University Hospital, Grenoble
Agency class:
Other
Collaborator:
Agency:
NETRIS Pharma
Agency class:
Industry
Source:
University Hospital, Grenoble
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05546879
