A Two Part Study of RO6870810. Dose-Escalation Study in Participants With Advanced Solid Tumors and Expansion Study in Participants With Selected Malignancies

January 3, 2018 updated by: Hoffmann-La Roche

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

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). RO6870810 is a small molecule, non-covalent inhibitor of bromodomain and extra-terminal (BET) family of bromodomains. This study is designed to characterize the safety, tolerability, pharmacokinetics and anti-tumor activity of RO6870810 in participants with histologically confirmed solid tumors with progressive disease (PD) which is refractory or intolerant to standard/approved therapies. In Part A, RO6870810 will be administered by subcutaneous (SC) injection daily for either 21 consecutive days in a 28-day cycle or for 14 consecutive days in a 21-day treatment cycle in participants with advanced solid tumor malignancies to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). In Part B, RO6870810 will be administered at a dose up to the MTD to further characterize the safety profile and biological effect in a subset of participants with advanced solid tumor malignancies. It is anticipated that a total of 84 participants will be enrolled in to this study (54 in Part A and 30 in Part B). In addition, it is expected that up to 20 participants with histologically confirmed nuclear protein in testis (NUT)-midline carcinoma (NMC) with progressive disease requiring therapy will be enrolled in the sub-study of Parts A and B. In addition, up to 20 participants with diffuse large B-cell lymphoma (DLBCL) may be enrolled at selected study sites.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

General:

  • Participants with solid tumors must have one or more metastatic tumors evaluable or measurable on radiographic imaging
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (or 2 upon approval by the medical monitor)
  • Life expectancy of greater than or equal to (>/=) 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

Advanced Solid Malignancies:

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

NUT-midline carcinoma:

  • Participants with histologically confirmed newly diagnosed or relapsed/refractory NMC with PD 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) Advanced Aggressive DLBCL
  • Histologically confirmed advanced aggressive B-cell lymphoma with abnormal MYC expression with persistent disease requiring treatment
  • Participants must have relapsed or progressed after at least 2 lines of prior therapy and not eligible for any curative treatment
  • Participants must have measurable disease

Exclusion Criteria:

  • Participants with hematologic malignancies
  • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia
  • Have Fridericia-corrected QT interval (QTcF) greater than (>) 470 milliseconds (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 human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibodies
  • History of major organ transplant
  • History of an autologous or allogeneic bone marrow transplant. For DLBCL participants only: DLBCL participants may have had a previous autologous transplant but not within 90 days of study entry
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RO6870810 (Part 1)
Participants will receive escalated doses of RO67870810 SC. RO6870810 will be escalated at a starting dose of 0.03 milligrams per kilogram (mg/kg) to a maximum of 0.85 mg/kg. Treatment will be administered in treatment cycles of either 21 days or 28 days and continued until PD, adverse events which justify treatment withdrawal, non-adherence, non-compliance, investigator decision, lost to follow-up, enrollment in other clinical study, or unacceptable toxicity.
Drug: RO6870810
Participants will receive RO6870810 at different planned doses with a starting dose of 0.03 mg/kg to a maximum dose of 0.85 mg/kg SC on Days 1 to 14 in a 21-day treatment cycle or on Days 1 to 21 in a 28-day treatment cycle.
Other Names:
  • TEN-010
Experimental: RO6870810 (Part 2)
Participants will receive RO6870810 at doses up to the MTD or up to the highest dose tested if the MTD is not defined. Treatment will be administered in treatment cycles of either 21 days or 28 days and continued until PD, adverse events which justify treatment withdrawal, non-adherence, non-compliance, investigator decision, lost to follow-up, enrollment in other clinical study, or unacceptable toxicity.
Drug: RO6870810
Participants will receive RO6870810 at different planned doses with a starting dose of 0.03 mg/kg to a maximum dose of 0.85 mg/kg SC on Days 1 to 14 in a 21-day treatment cycle or on Days 1 to 21 in a 28-day treatment cycle.
Other Names:
  • TEN-010

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Participants with DLTs
Time Frame: Day 1 up to Day 28 (or Day 21)
Day 1 up to Day 28 (or Day 21)
MTD of RO6870810
Time Frame: Day 1 up to Day 28 (or Day 21)
Day 1 up to Day 28 (or Day 21)
Percentage of Participants with Adverse Events
Time Frame: Baseline up to approximately 47 months
Baseline up to approximately 47 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area Under the Concentration Versus Time Curve from Time 0 (Pre-dose) to Time 24 Hours (AUC0-24) of RO6870810
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Pre-injection (Hour 0), immediately post-injection, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 24 and 28 hours post-injection on Day 1 Cycle 1; Pre-injection (Hour 0), immediately post-injection, 0.25, 0.5, 1, 2, and 4 hours post-injection on Day 15 Cycle 1; random samples on Days 8, 22 of Cycle 1 and on Day 1 of Cycle 2 and every cycle thereafter up to treatment completion (up to 47 months), end of treatment visit/early termination (up to 47 months) (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Maximum Plasma Concentration (Cmax) of RO6870810
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Pre-injection (Hour 0), immediately post-injection, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 24 and 28 hours post-injection on Day 1 Cycle 1; Pre-injection (Hour 0), immediately post-injection, 0.25, 0.5, 1, 2, and 4 hours post-injection on Day 15 Cycle 1; random samples on Days 8, 22 of Cycle 1 and on Day 1 of Cycle 2 and every cycle thereafter up to treatment completion (up to 47 months), end of treatment visit/early termination (up to 47 months) (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Time to Reach Cmax (Tmax) of RO6870810
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Pre-injection (Hour 0), immediately post-injection, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 24 and 28 hours post-injection on Day 1 Cycle 1; Pre-injection (Hour 0), immediately post-injection, 0.25, 0.5, 1, 2, and 4 hours post-injection on Day 15 Cycle 1; random samples on Days 8, 22 of Cycle 1 and on Day 1 of Cycle 2 and every cycle thereafter up to treatment completion (up to 47 months), end of treatment visit/early termination (up to 47 months) (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR]) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Screening up to PD/death whichever occurs first (assessed at screening, Day 1 of Cycle 1 and every odd numbered cycle up to treatment completion [up to 47 months], end of treatment visit [up to 47 months], and every 12 weeks thereafter up to study completion [up to 47 months]) up to 47 months (cycle length=21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Median Time Taken for the First Response Based on RECIST v 1.1 as Determined by the Investigator
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Screening up to PD/death whichever occurs first (assessed at screening, Day 1 of Cycle 1 and every odd numbered cycle up to treatment completion [up to 47 months], end of treatment visit [up to 47 months], and every 12 weeks thereafter up to study completion [up to 47 months]) up to 47 months (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Median Time Taken for the Best Overall Response Based on RECIST v 1.1 as Determined by the Investigator
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Screening up to PD/death whichever occurs first (assessed at screening, Day 1 of Cycle 1 and every odd numbered cycle up to treatment completion [up to 47 months], end of treatment visit [up to 47 months], and every 12 weeks thereafter up to study completion [up to 47 months]) up to 47 months (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Progression Free Survival Based on RECIST v 1.1 as Determined by the Investigator
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Screening up to PD/death whichever occurs first (assessed at screening, Day 1 of Cycle 1 and every odd numbered cycle up to treatment completion [up to 47 months], end of treatment visit [up to 47 months], and every 12 weeks thereafter up to study completion [up to 47 months]) up to 47 months (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Duration of Response Based on RECIST v 1.1 as Determined by the Investigator
Time Frame: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Screening up to PD/death whichever occurs first (assessed at screening, Day 1 of Cycle 1 and every odd numbered cycle up to treatment completion [up to 47 months], end of treatment visit [up to 47 months], and every 12 weeks thereafter up to study completion [up to 47 months]) up to 47 months (cycle length = 21 or 28 days)
Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Overall Survival
Time Frame: Screening up to death due to any cause (up to approximately 47 months)
Screening up to death due to any cause (up to approximately 47 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 16, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 11, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 11, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 12, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 19, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 5, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NP39141
  • TEN-010-001 (Other Identifier: Tensha)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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