A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)

Roche

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: [13C]-radiolabeled Idasanutlin; Drug: Idasanutlin; Drug: [14C]-radiolabeled Idasanutlin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02828930

2015-002532-40 (EudraCT Number)

NP29910

RG7388 (Other Identifier)

Details and patient eligibility

About

The purpose of this single-center, open-label, non-randomized study is to assess the excretion balance, pharmacokinetics, metabolism and absolute oral bioavailability of [14C]-labeled idasanutlin administered orally and [13C]-labeled idasanutlin administered intravenously in a single cohort of eligible participants. Participants will be screened for participation in this study within 21 days of receiving the first dose of study drug on Day 1. Treatment period will continue up to Day 28 after which participants will enter 28 day follow-up or the optional treatment extension of idasanutlin, depending on safety parameters and as per opinion of the Investigator.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, at the discretion of the Investigator
• Histologically or cytologically confirmed advanced malignancy, except leukemia and lymphoma
• Measureable or evaluable disease by Response evaluation criteria in solid tumors (RECIST) version 1.1, with no more than a single active malignancy in the previous 3 to 5 years prior to the administration of study drug
• Life expectancy of at least 12 weeks
• Participants taking opioid analgesics for pain should be on a stable pain and palliative care bowel regimen for one month prior to the first dose of study medication
• Adequate bone marrow, hepatic, and renal function
• Agreement to remain abstinent or use contraceptive methods specified in the study

Exclusion criteria

• History of any form of leukemia, except for Stage 0 - 1 chronic lymphocytic leukemia, not requiring treatment in addition to their underlying malignancy
• Have received hormonal therapy within the two weeks prior to the first dose of study drug
• Have pre-existing gastrointestinal disorders that may interfere with proper absorption of the drug
• History of seizure disorders or unstable Central Nervous System metastases (participants with stable CNS metastases allowed)
• Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Receive certain per protocol prohibited medications while on study. These medications must be discontinued 7 days prior to start of study drug
• Have bone marrow disorders, electrolyte imbalance, infrequent bowel movements (less than once per 48 hours), coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia
• Positive for human immunodeficiency virus currently receiving combination anti-retroviral therapy
• Regular work with ionizing radiation or radioactive material or treated with radiotherapy within 3 weeks prior to the first dose of study drug
• Refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Idasanutlin

Experimental group

Description:

On Day 1, 300 milligram (mg) idasanutlin tablet orally and 100 mg \[14C\]-radiolabeled idasanutlin capsule orally (2, 50 mg capsules containing approximately 100 microcurie of radioactivity). After 5 hours and 45 minutes of the oral dose, 100 microgram (mcg) of \[13C\]-radiolabeled idasanutlin will be administered over a 15-minute intravenous (IV) infusion. On Day 11, idasanutlin matching placebo aqueous dispersion orally and approximately after 1 hour, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. On Day 19, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days, and no treatment during 23 days of 28-day cycle, until the development of progressive disease, unacceptable toxicity, consent withdrawal or any other criteria for removal.

Treatment:

Drug: [14C]-radiolabeled Idasanutlin

Drug: Idasanutlin

Drug: Placebo

Drug: [13C]-radiolabeled Idasanutlin