A study to find the dose of INC280 combined with PDR001, which is tolerable and to test this dose as well as PDR001 alone in patients with advanced liver cancer
- Conditions
- hepatocellular carcinomaMedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005417-76-IT
- Lead Sponsor
- OVARTIS PHARMA SERVICES AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 90
1. Histologically or cytologically documented locally advanced recurrent
or metastatic HCC or for patients with cirrhosis clinical diagnosis of HCC
according to the American Association for the Study of Liver Diseases
(AASLD) and Asian Pacific Association for the Study of the Liver (APASL)
criteria. Current cirrhotic status of Child Pugh Class A (5-6 points), with no encephalopathy and/or clinically significant ascites (defined as
requiring diuretics or paracentesis treatment). Child Pugh status must
be calculated based on clinical and laboratory results during the
screening period.
2. Baseline tumor tissue (newly obtained) must be available at
screening. Patient must have a site of disease amenable to biopsy, and
be a candidate for tumor biopsy according to the treating institution's
guidelines and requirements for such procedure.
3. Patients must be willing to undergo a new tumor biopsy during the
study (6-9 weeks after start of study treatment, if medically feasible).
For patients in the phase II part of the study, exceptions may be granted
after documented discussion with Novartis. After a sufficient number of
paired biopsies are collected, the decision may be taken to stop
collecting the biopsies.
4. Patients must have received prior sorafenib treatment for HCC with
documented progression during or after discontinuation of sorafenib
treatment (for France only: patients must have received at least 8 weeks
of prior sorafenib treatment), or are intolerant to sorafenib (defined as
documented Grade 3 or 4 adverse events that led to sorafenib
discontinuation).
5. Patients must be tested during screening for Hepatitis-B-Virus surface
antigen (HbsAg) status. Patients are included in the study if they have
adequately controlled hepatitis B, defined by:
• receiving a nucleoside analog anti-viral drug for 3 or more months,
and
• serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level of
less than 100 IU/ml via polymerase chain reaction quantification assays
prior to enrollment.
Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65
1. Patient has received the following therapies prior to the first dose of study treatment:
• Previous systemic anti-cancer therapy (including therapeutic cancer vaccines and immunotherapeutics) other than sorafenib (sorafenib must be completed within > 2 weeks prior to the first dose of study treatment) or INC280.
• Previous locoregional therapy (e.g. hepatic arterial embolization, radio-frequency ablation, radiation therapy) if:
- administered after sorafenib treatment with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain.
Loco regional therapy for the focally painful liver tumor mass will be discussed on a case by case with Novartis.
- completed within 4 weeks prior to the dosing and, if present any related acute toxicity > grade 1.
2. Use of any live vaccines within 4 weeks of initiation of study treatment.
3. Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
4. Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment, unless agreed otherwise with
Novartis.
5. Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities or daily living or requiring therapeutic intervention).
6. Presence of CTCAE grade =1 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if CTCAE grade = 3) due to prior cancer therapy, unless agreed otherwise with Novartis.
7. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF) = 2 weeks prior start or study drug. An erythroid
stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is on a stable
dose.
8. History of severe hypersensitivity reactions to other mAbs.
9. Positive human immunodeficiency (HIV) testing at screening or Known history of testing positive for HIV or known acquired
immunodeficiency syndrome.
10. Clinically significant pleural effusion that either required pleurocentesis or is associated with shortness of breath.
11. Patients receiving treatment with medications that are strong inducers of CYP3A4 and that cannot be discontinued at least 1 week
prior to the start of treatment with INC280 and for the duration of the study.
12. Unable to stop herbal/food supplements or treatments which are considered to be capable of significantly causing either PK or PD
herb/food-drug interactions.
13. Active autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease or any condition
that requires systemic steroids or any immunosuppressive therapy, except vitiligo or resolved asthma/atopy that is treated with bronchodilators
(e.g., albuterol).
14. Clinically significant, uncontrolled heart diseases.
• Unstable angina within 6 months prior to screening
• Myocardial infarction within 6 months prior to screening
• History of documented congestive heart failure (New York Heart
Association functional classification III-IV)
• Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP)
= 160 mm Hg and/or Diastolic Blood Pressure (DBP) = 100 mm Hg, with
or without antihypertensive medication. Initiation or adjustment of
antihypertensive medication(s) is allowed prior to scree
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method