Clinical study on the use of a new treatment called BI 894999 administered orally once per day in patients with 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: 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)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]
- Registration Number
- EUCTR2015-001111-12-DE
- Lead Sponsor
- Boehringer Ingelheim Pharma GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 204
Pats. with solid tumours:
1. Confirmed diagnosis of 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. In Germany: Age >= 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 at the time of screening (up to 2 in NUT carcinoma).
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 start of treatment.
6. Male and female pats. WOCBP must to use highly effective methods of birth control per ICH M3(R2).
7. Written informed consent.
8. Optional written informed consent for tumour biopsies in the escalation phase Ia.
In addition, all pats. included in the expansion Phase Ib must have:
9. one of the four diagnoses: SCLC, mCRPC, CRC or NUT carcinoma.
10. failed conventional treatments or are not amenable to standard therapies (per crit.1) that specifically include for:
a. SCLC: a platinum-based therapy (previous treatment with topotecan not mandatory);
b. mCRPC: a hormonal agent (abiraterone, enzalutamide, apalutamide) and a taxane (docetaxel, cabazitaxel);
c. CRC: fluoropyrimidine, oxaliplatin and irinotecan, bevacizumab when applicable, and an EGFR inhibitor in RAS WT mCRC.
11. measurable disease acc. to RECIST 1.1 (not needed for NUT carcinoma pats.), or acc. to PCWG3 for the mCRPC cohort (see point 5 below, specific to mCRPC pats.).
12. progressive disease within the last 6 months, acc. to RECIST 1.1 or acc. to PCWG3 for the mCRPC cohort (see point 5 below, specific to mCRPC pats.).
13. 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 pats. or pats. with therapeutic INR). Biopsies are optional for NUT carcinoma pats.
14. given written informed consent for 2 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 pats. 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 LHRH agonist or antagonist, or by abiraterone, enzalutamide or apalutamide. If actual method of castration is LHRH agonsit or antagonist, the pat. must be willing to continue use of LHRH agonist or antagonist 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 described in point c below;
c. Increasing PSA level: at least 2 consecutive rising PSA values over a reference value (PSA no.1) taken at least 1 week apart. A third PSA (PSA no. 3) is required to be > than PSA no. 2; if not, a fourth PSA (PSA no. 4) is required to be > to PSA no. 2.
Pats. with solid tumours:
1. Inability to swallow tablets.
2. Additional other serious illness , concomitant disease, e.g. active SARS-COV-2 infection confirmed by PCR test, active Hep B with positive Hep B DNA test, active Hep C with positive Hep C RNA test, HIV infection (positive HIV diagnosis), or ongoing toxicity from prior therapies considered to potentially compromise pat.’s safety in this trial.
3. History or presence of cardiovascular abnormalities deemed clinically relevant 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 currently requiring another anti-cancer therapy.
6. Absolute neutrophil count < 1,500/mm3.
7. Platelet count < 100,000/mm3.
8. Bilirubin > 1.5 mg/dL (>26 µmol/L) (except known Gilbert’s syndrome: accepted up to 2 mg/dL or up to 34.2 µmol/L in this case).
9. AST and/or ALT > 2.5 times the ULN (in the presence of liver metastases, > 5 times the ULN).
10. Serum creatinine > 1.5 mg/dL (>132 µmol/L).
11. Women who are breastfeeding, pregnant or who plan to become pregnant while in the trial.
12. Previous treatment with a BET inhibitor (allowed only for NUT carcinoma pats.).
13. Treatment with other investigational drugs or participation in another clinical interventional trial within the past 4 wks (2 wks for NUT carcinoma pats.) 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 wks (2 wks for NUT carcinoma pats.) or 5 times the half-life of the drug, whichever is shorter (for NMC pats., washout for monoclonal antibodies must be discussed with the Sponsor). Radiotherapy given for curative intent within 4 wks 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 wks) used for palliative intent , bisphosphonates, denosumab, and to palliative radiotherapy (no washout required).
15. Pats. unable to comply with the protocol.
16. Pats. who are actively abusing alcohol or drugs. Since no alcohol or drug testing is required per protocol, it is at the investigator’s discretion to determine abuse.
Pats. with DLBCL:
1. Pat. 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 ULN (CTCAE grade 2 or higher).
8. Total bilirubin >1.5 x ULN (CTCAE grade 2 or higher).
9. Absolute neutrophil count <1,000/mm3 (without growth factor support).
10. Platelets <100,000/mm3 (without transfusions).
11. Serum creatinine 1.5 mg/dL (132 µmol/L).
12. Significant concurrent medical disease or condition which acc. to investigator’s judgement would either compromise pat. safety or interfere with the evaluation of the safety of the test drug, e.g. LVEF less than
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