Clinical trial NCT02076230: A Phase 1 TH-302 Mass Balance Trial
Official title: A Phase I, Open-Label, Two-Center Trial to Investigate the Mass Balance and Metabolite Profile of TH-302 in Cancer Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: 14C-TH-302
Advanced or Metastatic Solid Tumors
Evofosfamide
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Threshold Pharmaceuticals
First posted: 2014-03-03
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, Phase 1, two-center trial to evaluate the mass balance and metabolite profile of carbon 14 \[14C\]-labeled TH-302 (Label 1 and Label 2) followed by subsequent treatment with unlabeled TH-302 in cancer subjects with locally advanced or metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

* Male subject with pathologically or cytologically confirmed solid tumor which is locally advanced or metastatic, and either refractory to the standard therapy or for which no effective standard therapy is available
* Subject has measurable and evaluable disease as RECIST version 1.1
* Age greater than or equal to (\>=) 18 years and less than or equal to (=\<) 70 years
* Body mass index (BMI) \>= 19 and =\< 33 kilogram per square meter (kg/m\^2), body weight greater than (\>) 50 kilogram (kg)
* Eastern cooperative oncology group (ECOG) performance status of 0 to 1
* Life expectancy of at least 3 months
* At least 4 weeks from previous cytotoxic chemotherapy or radiation therapy and at least 5 half-lives or 6 weeks, whichever is longer, after targeted or biologic therapy
* Acceptable renal function, liver function and hematologic status as defined in the protocol
* Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

* New York Heart Association (NYHA) Class 3 or 4 congestive heart disease, myocardial infarction within 6 months, unstable arrhythmia, symptomatic ischemic heart disease or symptomatic peripheral arterial vascular disease
* Severe chronic obstructive or other pulmonary disease with hypoxemia as defined in the protocol
* Major surgery, other than diagnostic surgery, =\< 28 days prior to Day 1. Subject must have completely recovered from surgery
* Primary brain tumors or clinical evidence of active brain metastasis as defined in the protocol
* Treatment with strong inhibitors and/or inducers of drug metabolic enzymes or drug transporter as defined in the protocol
* Participation in a drug trial within 30 days prior to start of trial medication. Participation in a trial involving administration of 14C-labeled compound(s) within last 6 months prior to start of study drug
* Inability to understand the protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial
* Legal incapacity or limited legal capacity
* Other protocol-defined exclusion criteria could apply

Primary outcomes:
measure: Pharmacokinetics profile in plasma: Cmax, Tmax, AUC (0-t), lambda_z, t1/2, AUC (0-infinity), CL, Vss, Vz, MRT for TH-302 and its active metabolite Br-IPM
timeFrame: Days 1 and 8 of Cycle 1
measure: Pharmacokinetics profile in excreta: Cumulative Ae (0-t), Ae (0-infinity), percent radioactive dose excreted in urine and feces, AeUF, CLR, CLNR for TH-302 and its active metabolite Br-IPM
timeFrame: Day 1 of Cycle 1
Secondary outcomes:
measure: Number of subjects with Treatment-emergent adverse events (TEAEs)
timeFrame: Baseline up to Day 30 after the last dose of study treatment
measure: Blood to plasma ratio of total 14C-radioactivity
timeFrame: Days 1 and 8 of Cycle 1
measure: Total and free plasma concentrations of TH-302 in plasma
timeFrame: Day 1 of Cycle 1
measure: Number of subjects with tumor response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
timeFrame: Up to 1 year
measure: Unbound fraction (fu) of TH-302 in plasma
timeFrame: Day 1 of Cycle 1
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact the Merck KGaA Communication Center located in
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: