A Phase 1 TH-302 Mass Balance Trial

NCT02076230 | Completed Phase 1 DMC

• 2 other identifiers: EMR200592-0072013-003950-25
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor

Keywords

14C-TH-302; Advanced or Metastatic Solid Tumors; Evofosfamide

Outcome Measures

Primary Outcomes (2)

• 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

  Days 1 and 8 of Cycle 1

• 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

  Day 1 of Cycle 1

Secondary Outcomes (5)

• Number of subjects with Treatment-emergent adverse events (TEAEs)

  Baseline up to Day 30 after the last dose of study treatment

• Blood to plasma ratio of total 14C-radioactivity

  Days 1 and 8 of Cycle 1

• Total and free plasma concentrations of TH-302 in plasma

  Day 1 of Cycle 1

• Number of subjects with tumor response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)

  Up to 1 year

• Unbound fraction (fu) of TH-302 in plasma

  Day 1 of Cycle 1

Study Arms (2)

[14C] TH-302 (Label 1)

EXPERIMENTAL

Drug: [14C] TH-302 (Label 1); Drug: Unlabeled TH-302

[14C] TH-302 (Label 2)

EXPERIMENTAL

Drug: [14C] TH-302 (Label 2); Drug: Unlabeled TH-302

Interventions

[14C] TH-302 (Label 1) DRUG

\[14C\]-labeled TH-302 (Label 1) will be administered as intravenous infusion over 30 minutes on Day 1 of Part A.

[14C] TH-302 (Label 1)

[14C] TH-302 (Label 2) DRUG

\[14C\]-labeled TH-302 (Label 2) will be administered as intravenous infusion over 30 minutes on Day 1 of Part A.

[14C] TH-302 (Label 2)

Unlabeled TH-302 DRUG

Unlabeled TH-302 will be administered along with labeled TH-302 at the dose of 340 milligram per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1 of Part A, followed by recommended Phase 2 dose (RP2D) of 480 mg/m\^2 as monotherapy infusion over 30 minutes on Days 8 and 15 of Part A; and on Days 1, 8 and 15 of Part B, until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow up, or death.

[14C] TH-302 (Label 1); [14C] TH-302 (Label 2)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Threshold Pharmaceuticals: collaborator

Study Sites (1)

Please contact the Merck KGaA Communication Center located in

Darmstadt, Germany

Location

MeSH Terms

Interventions

TH 302

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2014
• First Posted: March 3, 2014
• Study Start: February 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: March 1, 2016
• Last Updated: June 10, 2016

Record last verified: 2016-06

Locations

DE (1)