Overview

This trial is active, not recruiting.

Condition neoplasms
Treatments bi 894999
Phase phase 1
Sponsor Boehringer Ingelheim
Start date July 2015
End date May 2017
Trial size 143 participants
Trial identifier NCT02516553, 1367.1, 2015-001111-12

Summary

The aim of the phase Ia (dose escalation) part of this trial is to assess the MTD of BI 894999 administered at escalating doses in two treatment schedules (schedule A of continuous dosing, schedule B with two weeks on treatment followed by one week off in 3-week cycles) in patients with solid tumours and for schedule A in Non-Hodgkin lymphoma patients. In the phase Ib expansion part, the aim is to further evaluate the safety profile of BI 894999 at the recommended dose and schedule in patients with solid tumours and to assess target modulation and the potential antitumour efficacy in patients with selected types of tumours. The PK profile will be determined from the first cycle in all patients in both phases.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
once daily continuous oral intake in 3-week cycles
bi 894999
day 1 to day 21 in 3-week cycles
(Experimental)
once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles
bi 894999
day 1 to day 14 followed by a week off in 3-week cycles in schedule B

Primary Outcomes

Measure
In phase Ib: Number of patients experiencing DLTs from start of treatment until end of treatment (in all cycles) as assessed approximately every 3 weeks after Cycle 2 (at the end of each new cycle) in order to determine the recommended phase II dose
time frame: average of 12 months
In phase Ia: Number of patients with DLT graded according to CTCAE v.4.03, observed in the first cycle (first 21 days) to meet the objective of assessing MTD of BI 894999 for each schedule in solid tumour patients and in schedule A in NHL patients
time frame: 3 weeks

Secondary Outcomes

Measure
efficacy endpoint in phases Ia and Ib: Objective Response (CR and PR) according to RECIST version 1.1 assessed by the investigator in the entire treatment period, for each Schedule in patients with solid tumours and for Schedule A in the NHL cohort
time frame: every 6 weeks, average of 4 months
efficacy endpoint in phases Ia and Ib: Disease control (CR, PR, SD) according to RECIST version 1.1 assessed by the investigator in the entire treatment period, for each Schedule in patients with solid tumours and for Schedule A in the NHL cohort
time frame: every 6 weeks, average of 4 months
efficacy endpoint in phase Ib: Progression-free Survival (PFS) with tumour assessment every 2 cycles (6 weeks if no delays) during the treatment period and until progression or death is reported
time frame: average of 5 months
efficacy endpoint in phase Ib: Best overall response with an evaluation of approximately every 2 cycles (6 weeks if no delays) during the entire treatment period
time frame: every 6 weeks, average of 4 months
In both phases: Cmax(,ss) after single and multiple dose of BI 894999, as measured during the first cycle (3 weeks)
time frame: 3 weeks
In both phases: AUC0-24 after single and multiple dose of BI 894999, as measured during the first cycle (3 weeks)
time frame: 3 weeks
In both phases: AUC t after single and multiple dose of BI 894999, as measured during the first cycle (3 weeks)
time frame: 3 weeks
In phase Ia: Number of patients experiencing DLTs from start of treatment until end of treatment (in all cycles) for each schedule in patients with solid tumours and in schedule A in the NHL cohort as assessed approximately every 3 weeks after Cycle 2
time frame: average of 12 months
In both phases: Cmax after single and multiple dose of BI 894999, as measured during the first cycle (3 weeks)
time frame: 3 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria: For all patients 1. Age 18 years and older at the time of signature of the informed consent 2. Life expectancy of at least 12 weeks after the start of the treatment according to the investigator's judgement 3. 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) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. For women of chilbearing potential using a contraceptive pill, an additional barrier method is necessary due to the potential CYP3A4 inducing effect of BI894999. Male patients having a partner of childbearing potential must use condoms and ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least three months after the end of the trial - Any female who has experienced menarche and does not meet the criteria for "women not of childbearing potential" as described below. Women not of childbearing potential are defined as: women who are postmenopausal (12 months with no menses without an alternative medical cause) or who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy). 4. Written informed consent consistent with ICH-GCP and local legislation For patients with solid tumours 1. Patients with a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic solid tumour, who have failed conventional treatment or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies 2. Eastern Cooperative Oncology Group performance score 0 or 1 at the time of screening 3. Recovery of therapy-related toxicities from previous chemotherapy, tyrosine kinase inhibitors, hormone therapy, immunotherapy, antibodies, vaccine therapy, or radiotherapy to CTCAE < or =grade 1 (with the exception of alopecia, peripheral sensory neuropathy grade 2) 4. Written informed consent for tumour biopsies in the escalation phase Ia 1. optional for those patients until extension of the MTD cohort, 2. optional for the patients in the extension of MTD cohort at the same time points as described below for the expansion phase. For these patients in the extension of the MTD cohort, inclusion criterion 8 hereafter will be applicable In addition, all patients included in the expansion phase (part Ib) must: 5. have been diagnosed with one of the one to four types of tumours selected at the end of the escalation part. 6. have a measurable disease (radiated lesions do not qualify as target lesions) according to RECIST 1.1 7. have progressive disease within the last 6 months, according to RECIST 1.1 8. have a tumour lesion accessible for biopsies (pre- and at steady state under treatment in Cycle 1, ideally from the same anatomic lesion) 9. give written informed consent to tumour biopsies, one at screening and one after start of treatment, between Day 11 and Day 14 of Cycle 1 In patients with NHL 1.Patients with relapsed or refractory non-Hodgkin's lymphoma who have failed or who are not amenable to standard therapies but have an indication for therapy as per investigator's judgement 2. ECOG Performance Status 0, 1 or 2 at the time of screening 3. Measurable disease (radiated lesions do not qualify as target lesions) according to RECIST 1.1 4. Recovery of therapy-related toxicities from previous anti-lymphoma therapy to CTCAE <= grade 1 (with the exception of alopecia, peripheral sensory neuropathy grade 2) 5. written informed consent for tumour biopsies (optional) Exclusion criteria: For all patients: 1. Inability to swallow tablets 2. Second malignancy currently requiring another anti-cancer therapy 3. Serum creatinine greater than 1.5 mg/dL (>132 µmol/L, SI unit equivalent) 4. Women who are pregnant, nursing, or who plan to become pregnant while in the trial 5. Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks or within five times the half-life of the previous investigational drug, whichever is shorter, before start of therapy or concomitant with this trial 6. Patients unable to comply with the protocol 7. Patients 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. For patients with solid tumours: 1. Additional other serious illness , concomitant non-oncological disease (e.g. active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial 2. 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 3. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days before the start of treatment with BI 894999 4. Absolute neutrophil count less than 1500/mm3 5. Platelet count less than 100 000/mm3 6. Bilirubin greater than 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) 7. Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases, greater than five times the upper limit of normal) 8. Systemic anti-cancer therapy within four weeks or five times the half-life of the drug, whichever is shorter or other than palliative radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to Luteinizing hormone- releasing hormone (LHRH) agonists, steroids (given at a stable dose in the last four weeks) used for palliative intent, bisphosphonates and denosumab For patients with NHL: 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. High-dose therapy with stem cell support <3 months prior to visit 1 5. AST or ALT >2.5 x upper limit of normal (CTCAE grade 2 or higher) 6. Total bilirubin >1.5 x upper limit of normal (CTCAE grade 2 or higher) 7. Absolute neutrophil count <1.0 x 10^9/L(without growth factor support) 8. Platelets <100 x 10^9/L (without transfusions) 9. 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 the test drug, e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy with the exception of extra systoles or minor conduction abnormalities 10. Chronic or ongoing infection requiring treatment at the time of enrolment or within the previous two weeks, e.g. active infectious disease or known Hepatitis B/Hepatitis C infection, HIV 11. Systemic anti-NHL therapy within the past two weeks or five times the half-life of the drug, whichever is shorter (palliative radiotherapy and agents used for palliative reasons for example steroids (steroids must have been given at a stable dose in the last four weeks) and bisphosphonates, are allowed)

Additional Information

Official title 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
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.