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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Tensha Therapeutics
Sponsor:
Information provided by (Responsible Party):
Tensha Therapeutics
ClinicalTrials.gov Identifier:
NCT01987362
First received: November 5, 2013
Last updated: November 14, 2014
Last verified: November 2013
  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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Part, Phase 1, Multicenter, Open-label Study of 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 Tensha Therapeutics:

Primary Outcome Measures:
  • Maximum tolerated dose and dose-limiting toxicities as determined in Part A. [ Time Frame: End of Cycle 1 (Day 28) ] [ Designated as safety issue: Yes ]
    Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03).

  • Safety parameters [ Time Frame: Parts A and B: at a minimum Days 1, 8, 15, 22 of each treatment cycle. ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Cycle 1 Day 1, Day 8, Day 15, Cycle 2 Day 1, Day 15, Day 22. ] [ Designated as safety issue: No ]
    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.

  • Efficacy [ 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 ]
    Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1).


Estimated Enrollment: 66
Study Start Date: October 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

General

  • Patients with solid tumors must have one or more metastatic tumors evaluable or measurable on radiographic imaging
  • Ambulatory patients >= 18 years of age
  • ECOG performance status of 0 or 1 (or 2 upon approval by the medical monitor)
  • Life expectancy of >= 3 months
  • Disease-free of active second/secondary or prior malignancies >= 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
  • Provide written informed consent

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

Locations
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Andrew Wolanski    617-632-6623    andrew_wolanski@dfci.harvard.edu   
Principal Investigator: Geoff Shapiro, MD         
United States, Michigan
Karmanos Center Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Karen Forman, BAA, CCRP    313-576-8096    formank@karmanaos.org   
Principal Investigator: Muaiad Kittaneh, MD         
Sponsors and Collaborators
Tensha Therapeutics
Investigators
Study Director: Steve Landau, MD Tensha Therapeutics
  More Information

No publications provided

Responsible Party: Tensha Therapeutics
ClinicalTrials.gov Identifier: NCT01987362     History of Changes
Other Study ID Numbers: TEN-010-001
Study First Received: November 5, 2013
Last Updated: November 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tensha Therapeutics:
advanced solid tumors

ClinicalTrials.gov processed this record on November 27, 2014