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NCT Number: NCT01987362

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

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Key information

Conditions

Solid Tumors, Advanced Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Yale Cancer Center, New Haven, Connecticut, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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:
  • NUT Midline Carcinoma based on ectopic expression of NUT protein as determined by Immunohistochemistry (IHC) and/or;
  • 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

Treatment and study plan

RO6870810

Drug

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

Primary outcomes

  1. Number of Participants with DLTs

    Time frame: Day 1 up to Day 28 (or Day 21)

  2. MTD of RO6870810

    Time frame: Day 1 up to Day 28 (or Day 21)

  3. Percentage of Participants with Adverse Events

    Time frame: Baseline up to approximately 47 months

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. Overall Survival

    Time frame: Screening up to death due to any cause (up to approximately 47 months)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Nov 19, 2013
Registry last updated
Jan 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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