Clinical study on the use of a new treatment called BI 894999 administered orally once per day in patients with advanced malignancies
- Conditions
- MedDRA version: 21.1Level: 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]MedDRA version: 21.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10012820Term: Diffuse large B-cell lymphoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10010029Term: Colorectal cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)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 available
- Registration Number
- EUCTR2015-001111-12-DK
- Lead Sponsor
- Boehringer Ingelheim B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 204
In patients with solid tumours
1.confirmed diagnosis of advanced unresectable and/or metastatic, malignant solid tumour, which failed conventional treatment or with no therapy of proven efficacy, or not amenable to standard therapies
2.Age = adult legal age for the given country when signature of informed consent (ICF). For NC patients = 15 years when ICF (only adults in Germany and South Korea)
3.Oncology Group (ECOG) performance score 0 or 1 at the time of screening (up to 2 in NC)
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
6.both genders. Women of childbearing potential ready and able to use highly effective methods of birth control per ICH M3(R2)
7.Written ICF. For adolescent NC patients aged 15 to legal adult age, assent and ICF of the parents or legal guardian
8.Optional 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 NC
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 an EGFR inhibitor in RAS WT mCRC.
11.Have a measurable disease according to RECIST 1.1 (for NC 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 (not needed for NC patients) 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 NC 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 bone scan plus a rising PSA as descr
In patients with solid tumours
1.Inability to swallow tablets
2.Additional other serious illness , concomitant disease (e.g. active infectious disease including active infection with SARS-COV-2 confirmed by a PCR test or one in the prior 6 weeks 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 NC patients)
13.Treatment with other investigational drugs or participation in another interventional trial within the past 4 weeks (2 weeks for NC patients) 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 (2 weeks for NC patients) or 5 times the half-life of the drug, whichever is shorter. 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
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