A Study to Investigate the Bioequivalence or Relative Bioavailability of Three New Idasanutlin Tablet Variants Following Oral Administration in Participants With Solid Tumors

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03362723
• Other study ID #: NP39051
• Status: Completed
• Phase: Phase 1
• Start date: November 27, 2017
• Est. completion date: June 11, 2019

Study information

• Verified date: June 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 11, 2019
• Est. primary completion date: June 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Idasanutlin
Participants will receive one 300-mg dose of each of the four different oral tablet formulations of idasanutlin (tablet A [reference], B, C, D) during Cycle 1, in the order specified for their assigned treatment arm (Treatment Sequence 1-4). Participants who enter the optional treatment extension phase will receive the reference tablet formulation of idasanutlin, as specified in the Optional Treatment Extension Arm description.

Locations

Country	Name	City	State
Canada	Jewish General Hospital / McGill University	Montreal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
United States	University of Colorado	Aurora	Colorado
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	Yale Cancer Center; Medical Oncology	New Haven	Connecticut
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	University of Oklahoma Health Sciences Center; Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve (AUC) of Idasanutlin		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)
Primary	Maximum Observed Plasma Concentration (Cmax) of Idasanutlin		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	Time to Maximum Observed Plasma Concentration (tmax) of Idasanutlin		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	Apparent Clearance (CL/F) of Idasanutlin		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	Apparent Volume of Distribution (Vd/F) of Idasanutlin		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	Half-life (t1/2) of Idasanutlin		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	Percentage of Participants With Adverse Events		Baseline up to end of study (up to approximately 1.5 years)