An open label, Phase Ia/Ib dose finding study with BI 894999 orally administered once a day in patients with advanced malignancies, with repeated administration in patients with clinical benefit - BI 894999 first in human dose finding study in advanced malignancies
- Conditions
- Advanced, unresectable and/or metastatic solid tumours, which have failed with conventional treatment or for which no therapy of proven efficacy exists, or in patients who are not amenable to standard therapies and patients with diffuse large B-cell lymphoma (DLBCL) for whom there are limited or no standard treatment options availableMedDRA version: 20.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10012820Term: Diffuse large B-cell lymphoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10010029Term: Colorectal cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10078295Term: NUT midline carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-001111-12-BE
- Lead Sponsor
- SCS Boehringer Ingelheim Comm.V
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 158
In patients with solid tumours
1.confirmed diagnosis of an advanced unresectable and/or metastatic,
malignant solid tumour, which failed conventional treatment or for
which no therapy of proven efficacy exists, or not amenable to standard
therapies
2.Age = 18 years when signature of the informed consent(ICF). For NMC patients = 15 years when ICF (for Germany only = 18)
3.Oncology Group (ECOG) performance score 0 or 1 at the time of
screening (2 allowed in NMC)
4.Recovery of therapy-related toxicities from previous chemotherapy,
tyrosine kinase inhibitors, hormone therapy, immunotherapy, antibodies,
vaccine therapy, or radiotherapy to CTCAE = grade 1 (except for
alopecia, peripheral sensory neuropathy grade 2)
5.Life expectancy = 12 weeks after the start of the treatment
6.Male or female patients. Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3(R2)
7.Written ICF. For adolescent NMC patients aged 15 to < 18 years assent and ICF of the parents or legal guardian
8.Optional written ICF for tumour biopsies in the escalation phase Ia In addition, all patients included in the expansion Phase Ib must:
9.Have one of the four diagnoses: SCLC, mCRPC, CRC or NMC
10.Have failed conventional treatments or who are not amenable to standard therapies (per criterion 1) that specifically include for:
a.SCLC: a platinum-based therapy, (previous treatment with topotecan is not mandatory)
b.mCRPC: a hormonal agent (abiraterone, enzalutamide, or apalutamide)
and a taxane (docetaxel or cabazitaxel)
c.CRC: fluoropyrimidine, oxaliplatin and irinotecan, bevacizumab when applicable and EGFR inhibitor in RAS WT mCRC
11.Have a measurable disease according to RECIST 1.1 (for NMC patients
non-measurable disease only is acceptable) or according to PCWG3 for
the mCRPC cohort (see point 5 below, specific to mCRPC patients)
12.Have progressive disease within the last 6 months, according to
RECIST 1.1 or according to PCWG3 (R17-3377) for the mCRPC cohort
(see point 5 below, specific to mCRPC patients)
13.Have a tumour lesion accessible for biopsies (pre- and at steady state
under treatment in Cycle 1, ideally from the same anatomic lesion)
(except for mCRPC patients having only bone metastases or patients with therapeutic INR). Biopsies are optional for NMC patients
14.Give written ICF for two tumour biopsies, one at screening and one
after start of treatment, between Day 8 and Day 11 of Cycle 1 (when
applicable)
In addition, all patients in the mCRPC expansion cohort of Phase Ib must
have:
1.Histologically or cytologically confirmed adenocarcinoma of the
prostate
2.Radiographic evidence of metastatic prostate cancer (stage M1 or D2).
Distant metastases evaluable by bone scan, CT scan, or MRI within 28
days before the start of study treatment
3.PSA = 5 ng/mL (if no measurable disease by RECIST 1.1)
4.Prior surgical or chemical castration with a serum testosterone of <50
ng/dL (< 1.7 nmol/L) by luteinizing hormone releasing level hormone
(LHRH) agonist or antagonist or by abiraterone or by enzalutamide or
apalutamide. If the actual method of castration is LHRH agonist or
antagonist, the patient must be willing to continue its use during
protocol treatment
5.Progressive disease defined as at least one of the following:
a.Progressive measurable disease: using conventional solid tumour
criteria RECIST 1.1
b.Bone scan progression: at least two new lesions on bo
In patients with solid tumours
1.Inability to swallow tablets
2.Additional other serious illness , concomitant disease (e.g. active
infectious disease or active Hepatitis B with positive Hep B DNA test,
active Hep C infection with positive Hep C RNA test and HIV infection
(positive result in established HIV diagnosis assay), or ongoing toxicity
from prior therapies with the potential to compromise patient's safety in
this trial
3.History or presence of cardiovascular abnormalities deemed clinically
relevant by the investigator such as uncontrolled hypertension,
congestive heart failure NYHA classification of 3, unstable angina or
poorly controlled arrhythmia. Myocardial infarction within 6 months prior
to study entry. LVEF less than 50% at baseline.
4.Clinical evidence of symptomatic progressive brain or leptomeningeal
disease during the last 28 days before the start of treatment with BI
894999
5.Second malignancy requiring another anti-cancer therapy
6.Absolute neutrophil count <1500/mm3
7.Platelet count <100 000/mm3
8.Bilirubin>1.5 mg/dL (>26 µmol/L, SI unit equivalent) (except known
Gilbert's syndrome (accepted up to 2 mg/dL or up to 34.2 µmol/L in this
case)
9.Aspartate amino transferase (AST) and/or alanine amino transferase
(ALT) >2.5 times the upper limit of normal (ULN) (if liver metastases, >5
times ULN)
10.Serum creatinine >1.5 mg/dL (>132 µmol/L, SI unit equivalent)
11.Women who are breastfeeding, pregnant or who plan to become
pregnant during trial
12.Previous treatment with a BET inhibitor (allowed only for NMC
patients)
13.Treatment with other investigational drugs or participation in another
interventional trial within the past 4 weeks or within 5 times the half-life
of the previous investigational drug, whichever is the shorter, before
start of therapy or concomitant with this trial
14.Systemic anti-cancer therapy within 4 weeks or 5 times the half-life
of the drug, whichever is shorter (for NMC patients, washout for
monoclonal antibodies must be discussed with the sponsor).
Radiotherapy given for curative intent within the past 4 weeks before
start of therapy or concomitantly with this trial. These restrictions do not
apply to LHRH agonists or antagonists, steroids (given at a stable dose
in the last 4 weeks) used for palliative intent , bisphosphonates,
denosumab and to palliative radiotherapy (no wash out required)
15.Patients unable to comply with the protocol
16.Patients who are actively abusing alcohol or drugs (judgement of
abuse at investigator's discretion)
In patients with DLBCL
1.Patient is eligible for curative salvage high dose therapy followed by stem cell transplant.
2.Primary central nervous system (CNS) lymphoma or known CNS involvement
3.Prior allogeneic bone marrow or stem cell transplant
4.Second malignancy currently requiring another anti-cancer therapy
5.High-dose therapy with stem cell support <3 months prior to visit 1
6.Inability to swallow tablets
7.AST or ALT >2.5 x upper limit of normal (CTCAE grade 2 or higher)
8.Total bilirubin >1.5 x upper limit of normal (CTCAE grade 2 or higher)
9.Absolute neutrophil count <1.0 x 109/L (without growth factor support)
10.Platelets <100 x 109/L (without transfusions)
11.Serum creatinine > 1.5 mg/dL (132 µmol/L)
12.Significant concurrent medical disease or condition which according to the investigator's judgement would either compromise patient safety or interfere with the evaluation of the safety of
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