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Trial record 2 of 41 for:    TH-302

A Phase 1 TH-302 Mass Balance Trial

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Threshold Pharmaceuticals
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT02076230
First received: February 20, 2014
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Solid Tumor
Drug: [14C] TH-302 (Label 1)
Drug: [14C] TH-302 (Label 2)
Drug: Unlabeled TH-302
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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 [ Time Frame: Days 1 and 8 of Cycle 1 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Day 1 of Cycle 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of subjects with Treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Blood to plasma ratio of total 14C-radioactivity [ Time Frame: Days 1 and 8 of Cycle 1 ] [ Designated as safety issue: No ]
  • Total and free plasma concentrations of TH-302 in plasma [ Time Frame: Day 1 of Cycle 1 ] [ Designated as safety issue: No ]
  • Number of subjects with tumor response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Tumor response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to RECIST v 1.1.

  • Unbound fraction (fu) of TH-302 in plasma [ Time Frame: Day 1 of Cycle 1 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: February 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: [14C] TH-302 (Label 1) Drug: [14C] TH-302 (Label 1)
[14C]-labeled TH-302 (Label 1) will be administered as intravenous infusion over 30 minutes on Day 1 of Part A.
Drug: Unlabeled TH-302
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.
Experimental: [14C] TH-302 (Label 2) Drug: [14C] TH-302 (Label 2)
[14C]-labeled TH-302 (Label 2) will be administered as intravenous infusion over 30 minutes on Day 1 of Part A.
Drug: Unlabeled TH-302
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02076230

Locations
Germany
Please contact the Merck KGaA Communication Center located in
Darmstadt, Germany
Sponsors and Collaborators
Merck KGaA
Threshold Pharmaceuticals
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT02076230     History of Changes
Other Study ID Numbers: 200592-007, 2013-003950-25
Study First Received: February 20, 2014
Last Updated: September 10, 2014
Health Authority: Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines

Keywords provided by Merck KGaA:
14C-TH-302
Advanced or Metastatic Solid Tumors

ClinicalTrials.gov processed this record on November 25, 2014