A Dose Exploration Study With MK-8628 in Participants With Selected Advanced Solid Tumors (MK-8628-006)



Status:Terminated
Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:5/25/2017
Start Date:May 4, 2016
End Date:April 26, 2017

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A Phase IB Dose Exploration Trial With MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Subjects With Selected Advanced Solid Tumors

This is a study to determine the recommended dose of MK-8628 (formerly known as OTX015) for
further studies in participants with advanced nuclear protein in testis (NUT) midline
carcinoma (NMC), triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC),
or castration-resistant prostate cancer (CRPC). This is a two-part parallel study: Part A
will establish the recommended dose by evaluating dose limiting toxicity (DLT), safety,
discontinuation, and early efficacy and Part B will enroll participants with NMC only and
will evaluate safety and efficacy in this population.


Inclusion Criteria:

- Males and females ≥18 years of age for NSCLC, TNBC, and CRPC

- Males and females ≥16 years of age for NMC

- Diagnosis of one of the following advanced solid tumors for which standard therapy
either does not exist or has proven ineffective, intolerable or inacceptable for the
participant: NMC;TNBC; NSCLC; or CRPC

- Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1. CRPC participants may be enrolled with objective evidence of disease as
per Prostate Cancer Working Group (PCWG2) criteria

- Life expectancy ≥3 months

- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1

- Have an interval of ≥3 weeks (or ≥2 weeks for NMC participants) 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)

- CRPC participants must maintain ongoing androgen deprivation therapy with a
gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing
serum testosterone is <50 ng/dL (<1.7 nmol/L)

- Participants receiving bisphosphonate or denosumab therapy must be on stable doses
for at least 4 weeks before start of study therapy

- Females must not be pregnant (negative urine or serum human chorionic gonadotropin
test within 72 hours of study start)

- Females of childbearing potential and male participants must agree to use adequate
contraception starting with the first dose of trial treatment through 90 days after
the last dose of study medication

Exclusion Criteria:

- Has inability to swallow oral medications or presence of a gastrointestinal disorder
(e.g. malabsorption) deemed to jeopardize intestinal absorption of MK-8628

- Has persistent grade >1 clinically significant toxicities related to prior
antineoplastic therapies (except for alopecia). Stable sensory neuropathy ≤ grade 2
National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events
(CTCAE) Version 4.0 is accepted

- Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS
metastases. Treated and stable CNS metastases are allowed.

- History of prior or concomitant malignancies within 3 years of study start

- Have other serious illness or medical condition, such as active infection, unresolved
bowel obstruction, psychiatric disorders, or cerebrovascular accident within 1 year
of study start

- Known human immunodeficiency virus (HIV) and/or active Hepatitis B or C infections

- Have one of the following cardiac-related conditions: Congestive heart failure or
angina pectoris (except if medically controlled); myocardial infarction (within 1
year of study start); uncontrolled hypertension; or uncontrolled arrhythmias

- Other concomitant anticancer treatment

- Participation in another clinical trial or treatment with any investigational drug
(excluding anticancer treatments) within 30 days of study start

- Concomitant therapy with strong CYP3A4 inhibitors or inducers

- Therapeutic anticoagulation (e.g. warfarin, heparin, etc.) must be stopped at least 7
days prior to the first dose of MK-8628. Low-dose low molecular weight heparin (LMWH)
is permitted

- Is pregnant or breast-feeding
We found this trial at
4
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Boston, MA
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Brussels,
Phone: 32 2 776 60 28
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Brussels,
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Philadelphia, PA
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