Clinical trial NCT03338881: A Study to Assess Mass Balance, Pharmacokinetics (PK), and Metabolism of Orally Administered [14 C]-TAK-659 in Participants With Advanced Solid Tumor and/or Lymphoma Malignancies
Official title: A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of Orally Administered [14 C]-TAK-659 in Patients With Advanced Solid Tumor and/or Lymphoma Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Advanced Solid Neoplasms
Lymphoma Neoplasms
Keywords: Drug therapy
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2017-11-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the mass balance and to characterize the pharmacokinetics (PK) in plasma and urine, and of total radioactivity in plasma and whole blood following a single oral dose of \[14C\]-TAK-659 solution containing 60 to 80 micro curie (Ci) of total radioactivity in participants with advanced solid tumors and/or lymphomas.

Detailed description: The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat people who have advanced solid tumor and/or lymphoma malignancies. This study will look at the quantitative characterization of the mass balance, metabolic pathways, and rates and routes of excretion of TAK-659.

The study will enroll approximately 6 participants. The study will consist of 2 periods: absorption, distribution, metabolism, and excretion (ADME) study period and optional post-ADME study period. In ADME study period, participants will be assigned with \[14C\]-TAK-659 100 milligram (mg). After completion of ADME study period, participants may choose to continue in the optional post-ADME study period to receive TAK-659 100 mg.

This single center trial will be conducted in Netherlands. The overall time to participate in ADME study period will be 14 days and if participants choose the option to continue in the post-ADME study period, the maximum duration of participation will be 12 months, unless in the opinion of the investigator and sponsor the participant would derive benefit from continued treatment beyond 12 months. Participants will be followed up to 28 days after last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurs first.

Eligibility criteria: Key Inclusion Criteria:

1. Must have histologically or cytologically confirmed metastatic and/or advanced solid tumors and/or lymphomas for which standard curative or life-prolonging treatment does not exist or is no longer effective or tolerable.
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
3. Life expectancy of at least 3 months.
4. Suitable venous access for the study-required blood sampling (that is, PK).
5. Recovered (that is, grade less than or equal to \[\<=\] 1 toxicity) from the reversible effects of prior anticancer therapy (with the exception of alopecia and Grade 1 neuropathy).
6. Must have adequate organ function, including the following:

   * Adequate bone marrow reserve: absolute neutrophil count (ANC) greater than or equal to (\>=) 1000 per microliter (/mcL); platelet count \>=75,000/mcL (\>=50,000/mcL for participants with bone marrow involvement); and hemoglobin \>=8 gram per deciliter (g/dL) (red blood cell \[RBC\] and platelet transfusion allowed \>=14 days before assessment).
   * Hepatic: total bilirubin \<=1.5 times the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<=2.5\*ULN.
   * Renal: creatinine clearance \>=60 milliliter per minute (mL/min) either as estimated by the Cockcroft-Gault equation or based on urine collection

Key Exclusion Criteria:

1. Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or computed tomography (CT) scan/magnetic resonance imaging (MRI).
2. Known human immunodeficiency virus (HIV) positivity or HIV-related malignancy.
3. Systemic anticancer treatment (including investigational agents) or radiotherapy within 3 weeks before the first dose of study treatment \<=5 times the half-life for large molecule agents or \<=4 weeks with evidence of progressive disease if 5 times the half-life is greater than (\>) 4 weeks.
4. Use or consumption of any of the following substances:

   * Medications or supplements that are known to be inhibitors of P-glycoprotein (P-gp) and/or strong reversible inhibitors of cytochrome P450 (CYP) 3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known), or within 7 days (if a reasonable half-life estimate is unknown), before the first dose of study drugs
   * Medications or supplements that are known to be strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers within 7 days or within 5 times the inhibitor or inducer half-life (whichever is longer) before the first dose of study drugs. In general, the use of these agents is not permitted during the study except when an AE must be managed during interruption of study drug dosing.
   * Food or beverages containing grapefruit within 5 days before the first dose of study drugs. Note that food and beverages containing grapefruit are not permitted during the study.
5. Ongoing nausea or vomiting that is Grade 2 or worse in intensity.
6. Systemic infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
7. Active secondary malignancy that requires treatment. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry.
8. Irregular defecation patterns and/or history of urinary and/or fecal incontinence.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-659
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity for [14C]-TAK-659
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-659
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for TAK-659
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve from Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-659
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: Ae urine,14C: Cumulative Amount of Radioactivity Excreted in Urine for [14C]-TAK-659
timeFrame: Baseline up to 14 days
measure: Ae feces, 14C: Cumulative Amount of Radioactivity Excreted in Feces for [14C]-TAK-659
timeFrame: Baseline up to 14 days
measure: Ae total: Total Cumulative Amount of Radioactivity Excreted in Urine and Feces for [14C]-TAK-659
timeFrame: Baseline up to 14 days
measure: Ae urine: Cumulative Amount of TAK-659 Excreted in Urine
timeFrame: Baseline up to 14 days
measure: Percentage of Dose Excreted in Urine for TAK-659
timeFrame: Baseline up to 14 days
measure: Renal Clearance (CLR) of TAK-659
timeFrame: Baseline up to 14 days
Secondary outcomes:
measure: Percentage of TAK-659 Metabolites in Plasma
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: Percentage of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of Participants with Grade 3 or Higher Adverse Events (AEs)
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of Participants with Drug Related AEs
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of Participants with Drug Related Grade 3 or Higher AEs
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of Participants with AEs Leading to Discontinuation of TAK-659
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
timeFrame: Baseline up to 28 days after the last dose of study drug (Week 58)
measure: Percentage of TAK-659 Metabolites in Urine and Feces
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Other outcomes:
Locations:
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: