Clinical trial NCT03991494: Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Pamiparib in Participants With Advanced Cancer
Official title: A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]Pamiparib Following Single Oral Dose Administration in Patients With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-06-19
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is an open-label study, in participants with advanced and/or metastatic solid tumors, which consists of 2 parts: a research phase (inpatient) and a treatment phase. The research phase (Part 1) of the study will assess the disposition of a single oral dose of \[14C\]-pamiparib. In the treatment phase (Part 2) participants will be allowed to have continued access to pamiparib.


Eligibility criteria: Key Inclusion Criteria:

1. Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with approved therapies for which there are no standard therapies available
2. A total body weight between 50 and 100 kg, inclusive at Screening
3. Measurable disease by CT/MRI
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
5. Adequate organ function

Key Exclusion Criteria:

1. Clinically significant cardiovascular disease
2. Have a previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease causing malabsorption syndrome.
3. Poor peripheral venous access
4. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 2 weeks prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
5. Use or have anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Plasma Pamiparib Pharmacokinetics: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to Infinity (AUC0-∞)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC-t)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: Maximum Observed Concentration (Cmax) of Pamiparib
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Maximum Observed Concentration (Cmax)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: Time of Cmax (Tmax)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Total Radioactivity Whole Blood Total Radioactivity Pharmacokinetics: Time of Cmax (Tmax)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: Apparent Total Clearance (CL/F)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: Apparent Volume of Distribution (Vz/F)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pamiparib Pharmacokinetics: AUC0-∞ of Plasma Pamiparib Relative to AUC0-∞ of Plasma Total Radioactivity
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Plasma Pharmacokinetics: AUC0-∞ of Whole Blood Total Radioactivity to AUC0-∞ of Plasma Total Radioactivity
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7
measure: Percentage of Total Radioactivity Excreted in Urine
timeFrame: 192 hours of [14C]-Pamiparib Administration
measure: Cumulative Urinary Excretion of Pamiparib
timeFrame: 192 hours of [14C]-Pamiparib Administration
measure: Renal Clearance of Pamiparib (CLR)
timeFrame: 192 hours of [14C]-Pamiparib Administration
measure: Fecal Recovery of Total Radioactivity
timeFrame: 192 hours of [14C]-Pamiparib Administration
measure: Cumulative Recovery of Total Radioactivity in Total Excreta
timeFrame: 192 hours of [14C]-Pamiparib Administration
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2
timeFrame: Up to 6 months
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Up to 6 months
measure: Number of Participants With Clinically Significant Abnormalities in 12-lead ECG Parameters, Vital Signs Data, Physical Examinations and Weight Data
timeFrame: Up to 6 months
measure: Pamiparib Metabolite Identified and Metabolic Profile Using Measured Mass (M3)
timeFrame: 0.5, 1, 2, 6, 12, 24, 48, 72, 96, 120, and 144 hours post dose on Days 1 to 7
Other outcomes:
Locations:
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
state: Wirral
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital Clinical Research Unit
Study officials:
affiliation: BeiGene
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mu S, Palmer D, Fitzgerald R, Andreu-Vieyra C, Zhang H, Tang Z, Su D, Sahasranaman S. Human Mass Balance and Metabolite Profiling of [14 C]-Pamiparib, a Poly (ADP-Ribose) Polymerase Inhibitor, in Patients With Advanced Cancer. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1108-1120. doi: 10.1002/cpdd.943. Epub 2021 Apr 19.