AzTrials
AzTrials

NeoplasmsPhase 1NCT02558140

A Dose Escalation Study of RO6874813 in Participants With Locally Advanced or Metastatic Solid Tumors

A Phase 1 study testing RO6874813 in people with Neoplasms, run by Hoffmann-La Roche at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This first-in-human study consists of three parts. The primary purpose of Part 1 is to characterize the safety and tolerability of RO6874813 in participants with locally advanced and/or metastatic solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
RO6874813
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
4 sitesin 3 countries
Study dates
11 Oct 2015to 6 Nov 2017
Phase
Phase 1
Are there results?
None posted in the registry

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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part 1: Participants with histologically/cytologically confirmed locally advanced or metastatic, non-resectable solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists
  • Part 2: Participants with histologically/ cytologically confirmed locally advanced or metastatic, non-resectable solid tumors known to be FAP+ whose disease has progressed despite standard therapy or for whom no standard therapy exists
  • Part 3: Participants with histologically confirmed recurrent or metastatic, non-resectable confirmed FAP+ sarcoma with two or fewer prior regimens for advanced disease
  • All participants must have tumor tissue that can be imaged for pharmacodynamic assessments and from which a pre- and on-treatment biopsy can be safely obtained
  • An archival tumor sample must be available for retrospective FAP expression analysis
  • Measurable disease as determined by RECIST v1.1
Show all 9Show fewer
  • World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
  • Recovery from all reversible AEs of previous anti-cancer therapies to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade 1, except for alopecia (any grade) and Grade <=2 sensory peripheral neuropathy
  • Negative pregnancy test

Who cannot join

  • Primary central nervous (CNS) tumors or CNS tumor involvement
  • Major surgery or any other prior anti-cancer treatment within 4 weeks prior to study Day 1.
  • Received wide-field radiotherapy <= 4 weeks or limited-field radiotherapy <=2 weeks prior to starting study drug
  • Known hypersensitivity to any of the components of RO6874813 or to the contrast agents used in the study
  • Another invasive malignancy in the last 2 years except for those with a minimal risk of metastasis or death
  • Any other conditions or diseases that would contraindicate participation in the clinical study because of safety concerns or compliance with clinical study procedures

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

Spain2 sites
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

    Madrid, 28050

Other trials in Spain

United States1 site
  • SCRI

    Nashville, Tennessee, 37203

Other trials in United States

France1 site
  • Centre Leon Berard; Departement Oncologie Medicale

    Lyon, 69373

Other trials in France

About this study

Official title: An Open-Label, Multicenter, Dose-Escalation Phase I Study of RO6874813, Administered Intravenously in Patients With Locally Advanced or Metastatic Solid Tumors

This first-in-human study consists of three parts. The primary purpose of Part 1 is to characterize the safety and tolerability of RO6874813 in participants with locally advanced and/or metastatic solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. In addition, the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) will be determined. In Part 2 the safety and tolerability of RO6874813 will continue to be characterized in participants with locally advanced and/or metastatic solid tumors known to be fibroblast activation protein-alpha positive (FAP+). In addition, treatment-induced efficacy of RO6874813 will be assessed by functional imaging and paired tumor biopsies. The primary purpose of Part 3 is to demonstrate anti-tumor activity of RO6874813 in participants with recurrent or metastatic FAP+ sarcomas.

Conditions
Neoplasms
Being tested
RO6874813
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO6874813Biological

    RO6874813 will be administered at a single low dose of 0.5 mg/kg via IV infusion in a 7- day PK run-in period (Cycle 0). Dose level for RO6874813 will be escalated to determine MTD and RP2D for RO6874813.

  • RO6874813Biological

    RO6874813 at RP2D will be administered by IV infusion as per dosing schedule determined in Part 1.

Study groups in NCT02558140
Study groupRoleWhat they receive
Part 1: Dose EscalationExperimentalAll participants will be given RO6874813 as a single low dose of 0.5 milligrams per kilogram (mg/kg) via intravenous (IV) infusion in a 7-day pharmacokinetic (PK) run-in period (Cycle 0). This is followed by dose escalation (Cycle 1) for which participants will receive escalating doses of RO6874813 (starting dose = 1 mg/kg) via IV infusion every week (qw) or every 2 weeks (Q2W) for 28 to 42 days to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).
Receives: Biological: RO6874813
Part 2: Tumor Biopsy and ImagingExperimentalThe first 15 participants with fibroblast activation protein-alpha positive (FAP+) tumors will be treated at the RP2D and dosing schedule as determined in Part 1, and will undergo paired tumor biopsies for biomarker assessments. Up to 5 participants with FAP+ tumors will undergo baseline and on-treatment tumor biopsies for biomarker assessments at a dose below the RP2D. The dose for these participants can be escalated to RP2D after 4 weeks of treatment and upon completion of biomarker assessment.
Receives: Biological: RO6874813
Part 3: Preliminary Efficacy AssessmentExperimentalParticipants with locally advanced or metastatic non-resectable FAP+ sarcoma will be treated with RO6874813 at the RP2D and as per schedule determined upon completion of Part 1. Participants continuing treatment with RO6874813 beyond 36 weeks will enter the extension phase of Part 3 and will be monitored for disease status and clinical safety per routine standard of care.
Receives: Biological: RO6874813

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Percentage of Participants With Dose-Limiting Toxicity (DLT)

    Measured: 28 days

  2. Part 1: Maximum Tolerated Dose (MTD) of RO6874813

    Measured: 28 days

  3. Part 1: Recommended Phase 2 Dose (RP2D) of RO6874813

    Measured: 28 days

  4. Parts 1 and 2: Percentage of Participants With Adverse Events (AEs)

    Measured: Baseline up to approximately 24 months

  5. Parts 1 and 2: Percentage of Participants With Anti-Drug Antibodies (ADAs)

    Q2W (1 cycle=14 days): Predose (Hr 0) on Day 1 of Run-in period (Part 1 only), Cycles 1, 3, 5, then every 2 cycles (up to approximately 12 months); QW (1 cycle=7 days): Predose on Day 1 of Run-in period (Part 1 only), Cycles 1, 2, 5, then every 2 cycles (up to approximately 12 months)

    Measured: Predose (Hour [Hr] 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame

  6. Part 3: Percentage of Participants With Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Measured: Baseline until disease progression (up to approximately 12 months)

  7. Part 3: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  8. Part 3: Duration of Response (DoR) as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  9. Part 3: Median Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  10. Part 3: Percentage of Participants Who are Progression-Free at Months 3 as Determined by the Investigator Using RECIST v1.1

    Measured: Month 3

  11. Part 3: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1

    Measured: Month 6

  12. Part 3: Median Overall Survival (OS)

    Measured: Baseline until death (up to approximately 24 months)

  13. Part 3: Percentage of Participants Who are Alive at Month 12

    Measured: Month 12

Secondary outcomes (18)
  1. Parts 1, 2, and 3: Maximum Observed Serum Concentration (Cmax) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), End of Infusion (EoI) (infusion length less than or equal to [<=] 1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  2. Parts 1, 2, and 3: Minimum Observed Serum Concentration (Cmin) of RO6874813

    Measured: QW or Q2W: Predose (Hr 0) on Day 1 in Cycles 0, 1, 2, 3, 4, 5, 6, 7, and every 2 cycles thereafter (up to approximately 12 months)

  3. Parts 1, 2, and 3: Time to Reach Cmax (Tmax) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  4. Parts 1, 2, and 3: Half-Life (t1/2) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  5. Parts 1, 2, and 3: Area Under the Concentration-Time Curve (AUC) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  6. Parts 1, 2, and 3: Clearance (CL) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  7. Parts 1, 2, and 3: AUC During One Dose Interval (AUCtau) of RO6874813

    Measured: Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycle 1 and QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycle 1

  8. Parts 1, 2, and 3: Volume at Steady State (Vss) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  9. Parts 1, 2, and 3: Accumulation Ratio (RA) of RO6874813

    Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months)

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  10. Parts 1, 2, and 3: Observed Steady-State Concentration at the End of a Dosing Interval (Ctrough) of RO6874813

    Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycle 1. QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycle 1

    Measured: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

  11. Parts 1, 2, and 3: Change from Baseline in Body Weight Corrected Maximum Standardized Uptake Volume (SUVmax) as Measured by 2-[18F]Fluoro-2-Deoxyglucose Positron Emission Tomography ([18F]-FDG PET)

    Measured: Baseline and 12 months

  12. Part 1 and 2: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  13. Part 1 and 2: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  14. Part 1 and 2: DOR as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  15. Part 1 and 2: Median PFS as Determined by the Investigator Using RECIST v1.1

    Measured: Baseline up to approximately 12 months

  16. Part 1 and 2: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1

    Measured: Month 6

  17. Part 3: Percentage of Participants With AEs

    Measured: Baseline up to approximately 24 months

  18. Part 3: Percentage of Participants With ADAs

    Q2W (1 cycle=14 days): Predose (Hr 0) on Day 1 of Run-in period (Part 1 only), Cycles 1, 3, 5, then every 2 cycles (up to approximately 12 months); QW (1 cycle=7 days): Predose on Day 1 of Run-in period (Part 1 only), Cycles 1, 2, 5, then every 2 cycles (up to approximately 12 months)

    Measured: Predose (Hr 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2015 (estimated)
  2. Study start11 Oct 2015
  3. Primary completion6 Nov 2017
  4. Study completion6 Nov 2017

Resources

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
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02558140
Sponsor's protocol ID
BP29773
Other IDs
RG7386, 2015-001889-26, 2015
Status last verified
Apr 2018
First submitted
15 Sep 2015
Last updated
4 Apr 2018
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO6874813 in people with Neoplasms, run by Hoffmann-La Roche at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Spain, United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Percentage of Participants With Dose-Limiting Toxicity (DLT) (time frame: 28 days). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2018.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in