Solid Tumors, Advanced Solid TumorsPhase 1NCT01987362
A Two Part Study of RO6870810. Dose-Escalation Study in Participants With Advanced Solid Tumors and Expansion Study in Participants With Selected Malignancies
A Phase 1 study testing RO6870810 in people with Solid Tumors, Advanced Solid Tumors, run by Hoffmann-La Roche at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Solid Tumors, Advanced Solid Tumors
- What is being tested?
- RO6870810
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 4 sitesUnited States
- Study dates
- 16 Oct 2013to 11 Oct 2017
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Karmanos Cancer Center
Detroit, Michigan, 48201
Yale Cancer Center
New Haven, Connecticut, 06520
About this study
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
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.
- Conditions
- Solid Tumors, Advanced Solid Tumors
- Being tested
- RO6870810
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO6870810Drug
Also called TEN-010
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.
| Study group | Role | What they receive |
|---|---|---|
| RO6870810 (Part 1) | Experimental | 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. Receives: Drug: RO6870810 |
| RO6870810 (Part 2) | Experimental | 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. Receives: Drug: RO6870810 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with DLTs
Measured: Day 1 up to Day 28 (or Day 21)
MTD of RO6870810
Measured: Day 1 up to Day 28 (or Day 21)
Percentage of Participants with Adverse Events
Measured: Baseline up to approximately 47 months
Secondary outcomes (9)
Area Under the Concentration Versus Time Curve from Time 0 (Pre-dose) to Time 24 Hours (AUC0-24) of RO6870810
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)
Measured: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Maximum Plasma Concentration (Cmax) of RO6870810
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)
Measured: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Time to Reach Cmax (Tmax) of RO6870810
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)
Measured: 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
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)
Measured: 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
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)
Measured: 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
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)
Measured: 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
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)
Measured: 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
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)
Measured: Baseline up to 47 months (detailed timeframe is provided in the outcome description)
Overall Survival
Measured: Screening up to death due to any cause (up to approximately 47 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2013 (estimated)
- Study start16 Oct 2013
- Primary completion11 Oct 2017
- Study completion11 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumors, Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01987362
- Sponsor's protocol ID
- NP39141
- Other IDs
- TEN-010-001
- Status last verified
- Jan 2018
- First submitted
- 5 Nov 2013
- Last updated
- 5 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Shapiro GI, LoRusso P, Dowlati A, T Do K, Jacobson CA, Vaishampayan U, Weise A, Caimi PF, Eder JP, French CA, Labriola-Tompkins E, Boisserie F, Pierceall WE, Zhi J, Passe S, DeMario M, Kornacker M, Armand P. A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma. Br J Cancer. 2021 Feb;124(4):744-753. doi: 10.1038/s41416-020-01180-1. Epub 2020 Dec 14.
PubMed 33311588