A Dose-Finding Study of Birabresib (MK-8628), a Small Molecule Inhibitor of the Bromodomain and E… (NCT02259114) | Clinical Trial Compass
CompletedPhase 1
A Dose-Finding Study of Birabresib (MK-8628), a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Adults With Selected Advanced Solid Tumors (MK-8628-003)
47 participantsStarted 2014-10-23
Plain-language summary
Open-label, phase I, non-randomized, multicentric study of single-agent birabresib (MK-8628) (formerly known as OTX015) administered according to two distinct regimens to participants with selected advanced tumors.
The study will be performed in two parts.
Dose Escalation Part:
This step is designed to determine the maximum tolerated dose (MTD) in each of the two regimens, which will be evaluated in parallel. Participants will receive oral birabresib according to:
Continuous Dosing Regimen: continuous, once daily for 21 consecutive days (21-day cycles).
OR Days 1-7 Dosing Regimen: once daily on Days 1 to 7, repeated every 3 weeks (21-day cycles; 1 week ON/2 weeks OFF).
Participants will be sequentially assigned to Continuous Dosing Regimen or Days 1-7 Dosing Regimen according to the next available place and receive birabresib at escalating doses levels (DL). Cohorts of 3 participants will be treated, and an additional 3 participants will be treated at the first indication of dose-limiting toxicity (DLT). MTD assessment will be based on the tolerability observed during the first 21 days of treatment.
Expansion Part:
The efficacy of birabresib in each of the five indications (i.e., Bromodomain-Nuclear Protein in Testis \[BRD-NUT\] midline carcinoma, triple negative breast cancer \[TNBC\], non-small cell lung cancer \[NSCLC\] harboring a rearrangement Anaplastic Lymphoma Kinase \[ALK\] gene/fusion protein or Kirsten Ras \[KRAS\] mutation, castrate-resistant prostate cancer, and pancreatic ductal carcinoma) will be assessed in terms of response (Response Evaluation Criteria in Solid Tumors v1.1 \[RECIST v1.1\] or Prostate Cancer Clinical Trials Working Group 2 \[PCWG2\]) using a selected regimen.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Signed informed consent obtained prior to initiation of any study-specific procedures and treatment;
. Histologically or cytologically confirmed diagnosis of one of the following advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective, intolerable or inacceptable for the patient:
. At least one measurable lesion as per RECIST version 1.1., except for CRPC participants who may be enrolled with objective evidence of disease as per PCWG2 criteria;
. Age ≥18 years at the time of informed consent;
. Life expectancy ≥3 months;
. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1;
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
Timeframe: Up to Cycle 1 Day 21 (Up to 21 days)
Trial details
NCT IDNCT02259114
SponsorOncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
. Adequate bone marrow reserve, renal and liver function:
. An interval of ≥3 weeks since chemotherapy (≥6 weeks for nitrosoureas or mitomycin C), immunotherapy, hormone therapy or any other anticancer therapy or surgical intervention resection, or ≥3 half-lives for monoclonal antibodies, or ≥5 half-lives for other non-cytotoxic agents (whichever is longer);
Exclusion criteria
. Inability to swallow oral medications or presence of a gastrointestinal disorder (e.g. malabsorption) deemed to jeopardize intestinal absorption of birabresib;
. Persistent grade \>1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0 is accepted.
. Known primary central nervous system (CNS) malignancy or CNS involvement;
. History of prior or concomitant malignancies (other than excised non-melanoma skin cancer or cured in situ cervical carcinoma) within 3 years of study entry;
. Other serious illness or medical conditions, such as active infection, unresolved bowel obstruction, or psychiatric disorders;
. Known human immunodeficiency virus (HIV) positivity;
. Participation in another clinical trial or treatment with any investigational drug within 30 days prior to study entry;