Clinical trial NCT03362723: A Study to Investigate the Bioequivalence or Relative Bioavailability of Three New Idasanutlin Tablet Variants Following Oral Administration in Participants With Solid Tumors
Official title: A Multi-Center, Open-Label, Clinical Pharmacology Study for Idasanutlin, an MDM2 Antagonist With a Hybrid Randomized/Sequential, Single-Dose, 4-Period, Crossover Design to Investigate the Bioequivalence or Relative Bioavailability of Three New Idasanutlin Tablet Variants Following Oral Administration in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-12-05
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This multi-center, open-label, pharmacokinetic study will evaluate the bioequivalence (BE) or relative bioavailability (rBA) of three new idasanutlin-tablet variants compared to the reference tablet formulation following oral administration of a 300 milligrams (mg) dose in participants with solid tumors for whom no further treatment options are available. Following the four administrations of idasanutlin in the BE/rBA cycle of the study (Cycle 1), participants who have no clinically defined progressive disease and who recover from any prior treatment toxicity to Grade less than or equal to (\</=) 1 may enter the optional treatment extension phase. This extension phase will continue for additional 28-day cycles or until disease progression or unacceptable toxicity is observed.


Eligibility criteria: Inclusion Criteria:

* Participant must have histologically or cytologically confirmed advanced malignancies, except all forms of leukemia and lymphoma, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the participant
* Measureable or evaluable disease by RECIST v1.1 for solid tumors prior to the administration of study drug
* Ability to understand and willingness to sign a written informed consent form and comply with all study requirements
* Life expectancy of greater than or equal to (\>/=)12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* New York Heart Association (NYHA) status of less than or equal to (\</=)1
* Women of childbearing potential and men should remain abstinent or agree to use an effective form of contraception and to continue its use for the duration of study treatment and for a period of time after the last dose of study treatment
* Adequate bone marrow function, hepatic function, and renal function

Exclusion Criteria:

* Participants with prostate cancer who are unable to interrupt treatment with ketoconazole; ketoconazole treatment must be discontinued 2 weeks prior to first dose of study medication and is not allowed during Cycle 1, but may be used in the optional extension phase.
* Administration of investigational agents or investigational drugs \</=4 weeks or less than (\<)5 times the terminal half-life prior to study treatment start, whichever is longer
* Active gastrointestinal (GI) conditions and uncontrolled irritable bowel disease or pre-existing GI disorders that may interfere with proper absorption of the study drug
* History of allergic reactions attributed to components of the formulated product
* History of seizure disorders or unstable central nervous system metastases
* Presence of any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
* Evidence of electrolyte imbalance
* Pregnant or breast feeding
* Known coagulopathy, platelet disorder or history of non-drug-induced thrombocytopenia
* Current treatment with oral or parenteral anti-coagulants/antiplatelet agents
* Acute toxicities from any prior anti-tumor therapy, surgery, or radiotherapy that has not resolved to Grade \</=2, except alopecia
* Last dose of prior anti-tumor therapy \<21 days prior to the first administration of idasanutlin or \<5 times terminal half-life of that therapy, whichever is shorter
* Refusal to potentially receive blood products and/or have a hypersensitivity to blood products
* Known bone marrow disorders which may interfere with bone marrow recovery or participants with delayed recovery from prior chemoradiotherapy
* Planned procedure or surgery during the study
* History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
* Blood transfusion within 4 weeks prior to screening
* History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
* Current treatment with medications that are well known to prolong the QT interval

Primary outcomes:
measure: Area Under the Curve (AUC) of Idasanutlin
timeFrame: Predose (within 2 hours), 1, 2, 4, 6, and 10 hours on Days 1, 8, 15, and 22; on Days 2, 3, 5, 9, 10, 12, 16, 17, 19, 23, 24, and 26; Day 29 (end of Cycle 1) or Cycle 2 Day 1 (for participants in the optional treatment extension phase) (cycle=28 days)
measure: Maximum Observed Plasma Concentration (Cmax) of Idasanutlin
timeFrame: Predose (within 2 hours), 1, 2, 4, 6, and 10 hours on Days 1, 8, 15, and 22; on Days 2, 3, 5, 9, 10, 12, 16, 17, 19, 23, 24, and 26; Day 29 (end of Cycle 1) or Cycle 2 Day 1 (for participants in the optional treatment extension phase) (cycle=28 days)
Secondary outcomes:
measure: Time to Maximum Observed Plasma Concentration (tmax) of Idasanutlin
timeFrame: Predose (within 2 hours), 1, 2, 4, 6, and 10 hours on Days 1, 8, 15, and 22; on Days 2, 3, 5, 9, 10, 12, 16, 17, 19, 23, 24, and 26; Day 29 (end of Cycle 1) or Cycle 2 Day 1 (for participants in the optional treatment extension phase) (cycle=28 days)
measure: Apparent Clearance (CL/F) of Idasanutlin
timeFrame: Predose (within 2 hours), 1, 2, 4, 6, and 10 hours on Days 1, 8, 15, and 22; on Days 2, 3, 5, 9, 10, 12, 16, 17, 19, 23, 24, and 26; Day 29 (end of Cycle 1) or Cycle 2 Day 1 (for participants in the optional treatment extension phase) (cycle=28 days)
measure: Apparent Volume of Distribution (Vd/F) of Idasanutlin
timeFrame: Predose (within 2 hours), 1, 2, 4, 6, and 10 hours on Days 1, 8, 15, and 22; on Days 2, 3, 5, 9, 10, 12, 16, 17, 19, 23, 24, and 26; Day 29 (end of Cycle 1) or Cycle 2 Day 1 (for participants in the optional treatment extension phase) (cycle=28 days)
measure: Half-life (t1/2) of Idasanutlin
timeFrame: Predose (within 2 hours), 1, 2, 4, 6, and 10 hours on Days 1, 8, 15, and 22; on Days 2, 3, 5, 9, 10, 12, 16, 17, 19, 23, 24, and 26; Day 29 (end of Cycle 1) or Cycle 2 Day 1 (for participants in the optional treatment extension phase) (cycle=28 days)
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to end of study (up to approximately 1.5 years)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center; Medical Oncology
state: Connecticut
city: Saint Louis
country: United States
facility: Washington University; Wash Uni. Sch. Of Med
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
state: Nevada
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center; Stephenson Cancer Center
state: Oklahoma
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital / McGill University
state: Quebec
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: