A Two Part, Multicenter, Open-label Study of TEN-010 Given Subcutaneously

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01987362
First received: November 5, 2013
Last updated: August 8, 2016
Last verified: August 2016
  Purpose
TEN-010 is a small molecule, bromodomain and extra-terminal domain (BET) bromodomain inhibitor. This study is designed to characterize the safety, tolerability, pharmacokinetics and anti-tumor activity of TEN-010 in patients who are refractory or intolerant to standard/approved therapies. This first-in-human study of TEN-010 will be conducted in two parts: dose escalation and dose expansion. For dose escalation (Part A), a standard "3+3" design will be used in which successive cohorts of three or more patients with advanced solid tumor malignancies will be treated at escalating doses until a maximum tolerated dose (MTD) is identified. For the dose expansion part of the study (Part B), a subset of patients with advanced solid malignancies will be treated with TEN-010 at the MTD (or the highest dose tested if the MTD is not defined) to further characterize safety and biological effect. In addition, up to 10 patients with nuclear protein in testis (NUT) midline carcinoma (NMC) will be permitted to enroll in a substudy of the protocol. This is a Phase 1 non-randomized, dose-escalating, open label, multi-center study to be conducted in two parts (Part A and Part B). A maximum of 56 patients aged 18 years or older with histologically confirmed advanced solid tumors with progressive disease requiring therapy will be enrolled in the study. It is expected that approximately 36 patients will be enrolled in 6 cohorts of up to 6 patients per cohort in Part A of the study and 20 additional patients will be enrolled in Part B of the study. Up to 10 patients with NMC may be enrolled as part of a substudy within the protocol.

Condition Intervention Phase
Solid Tumors, Advanced Solid Tumors
Drug: TEN-010
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two-Part, Phase I, Multicenter, Open-Label Study of RO6870810/TEN-010 Given Subcutaneously: Part A: A Dose-Escalation Study in Patients With Advanced Solid Tumors. Part B: An Expansion Cohort in Patients With Selected Malignancies

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum tolerated dose and dose-limiting toxicities as determined in Part A\nToxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03) [ Time Frame: End of Cycle 1 (Day 28) ] [ Designated as safety issue: Yes ]
  • Safety parameters: Physical examination, clinical safety laboratory tests, assessment of adverse events, Eastern Cooperative Oncology Group Performance Status (ECOG PS), chest X-ray, Electrocardiogram (ECG), vital signs, and concomitant medication review [ Time Frame: Parts A and B: at a minimum Days 1, 8, 15, 22 of each treatment cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Plasma levels of TEN-010 will be measured during the treatment and follow-up periods. Pharmacokinetic variables to be calculated are AUC, Cmax, and Tmax [ Time Frame: Cycle 1 Day 1, Day 8, Day 15, Cycle 2 Day 1, Day 15, Day 22 ] [ Designated as safety issue: No ]
  • Efficacy: Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1) [ Time Frame: At baseline, at the end of Cycle 2 (2 months), and every 2 cycles (2 months) thereafter until disease progression or death ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment TEN-010 Drug: TEN-010
Safety, tolerability and pharmacokinetics of TEN-010 in Patients with Advanced Solid Malignancies.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

General:

  • Patients with solid tumors must have one or more metastatic tumors evaluable or measurable on radiographic imaging
  • Ambulatory patients > or = 18 years of age
  • ECOG performance status of 0 or 1 (or 2 upon approval by the medical monitor)
  • Life expectancy of > or = 3 months
  • Disease-free of active second/secondary or prior malignancies > or = 2 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
  • Adequate hematological, renal, hepatic and coagulation laboratory test results.
  • Women of child bearing potential and men must agree to use adequate contraception during the study and for 4 months after the last dose of study drug.
  • Available for the duration of the study and willing to follow study procedures

Advanced Solid Malignancies:

  • Patients with previously treated, histologically confirmed advanced solid malignancy with progressive disease requiring therapy
  • Patients must be refractory or intolerant to standard therapy

NUT-midline carcinoma:

  • Patients with histologically confirmed newly diagnosed or relapsed/refractory NUT-midline carcinoma (NMC) with progressive disease requiring therapy
  • Diagnosis of one of the following is required:

    1. NUT Midline Carcinoma based on ectopic expression of NUT protein as determined by Immunohistochemistry (IHC) and/or;
    2. Detection of NUT gene translocation as determined by Fluorescence In-Situ Hybridization (FISH).

Exclusion Criteria:

  • Patients with hematologic malignancies
  • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia
  • Have QTcF > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome
  • Active, uncontrolled bacterial, viral, or fungal infections
  • Known clinically important respiratory impairment
  • Positive for HIV, hepatitis B surface antigen, or hepatitis C antibodies
  • History of major organ transplant
  • History of an autologous or allogeneic bone marrow transplant
  • Symptomatic central nervous system malignancy or metastasis
  • Pregnant or nursing
  • Treatment with surgery or chemotherapy within 28 days prior to study entry
  • Prior treatment with small molecule (BET) family inhibitor
  • Radiation for symptomatic lesions within 14 days of study enrollment
  • Other exclusions 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: NCT01987362

Contacts
Contact: Reference Study ID Number: NP39141 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, Connecticut
Recruiting
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, Ohio
Recruiting
Beechwood, Ohio, United States, 44122
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01987362     History of Changes
Other Study ID Numbers: NP39141  TEN-010-001 
Study First Received: November 5, 2013
Last Updated: August 8, 2016
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on August 23, 2016