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CancerPhase 1NCT03786484

Study of PBF-999 in Solid Tumour Advanced Cancer

A Phase 1 study testing PBF-999 in people with Cancer, run by Palobiofarma SL at 1 site in Spain.

Completed

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

Official record
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Trial summary

Multicentric phase I (dose escalation plus expansion) clinical trial of PBF-999 in patients with immunotherapy naïve and pretreated solid tumors to evaluate the safety, tolerability and preliminary efficacy of the compound Read more about this study

Who is it for?
Any age
Conditions the study is for
Cancer
What is being tested?
PBF-999
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteSpain
Study dates
1 Oct 2017to 30 Jun 2022
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Advanced/metastatic histologically confirmed solid tumor
  • At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Patients who has progressed to the standard therapy
  • ECOG performance status of 0/1
  • Age greater than 18 years.
  • Adequate bone marrow, renal and hepatic function
  • Able and willing to give valid written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol (immune)therapy (not mandatory but highly recommended).
  • Prior immunotherapy is allowed

Who cannot join

  • Participation in another clinical study with an investigational product during the last 4 weeks or 5 half-lifes prior to starting on treatment.
  • Symptomatic and/or untreated Brain Metastases
  • Pregnancy or breast feeding
  • Serious uncontrolled medical disorder or active infection that in the investigator's opinion would impair the patient's ability to receive study treatment.
  • Concurrent use of other anticancer approved or investigational agents is not allowed.
  • Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
Show all 9Show fewer
  • Prior malignancy in past 2 years or as identified in Section 7.2 of this protocol
  • Patients receiving systemic steroids ≥ 10mg/day of prednisone or the equivalent
  • Concurrent administration of strong inhibitors or moderate inducers of CYP1A2 is not permitted; administration must be discontinued at least 7 days prior to initiating study drug administration.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Vall d'Hebron institute of oncology (VHIO)

    Barcelona

Other trials in Spain

About this study

Official title: Phase I/Ib Trial of Single Agent PBF-999 in Solid Tumour Advanced Cancer

Multicentric phase I (dose escalation plus expansion) clinical trial of PBF-999 in patients with immunotherapy naïve and pretreated solid tumors to evaluate the safety, tolerability and preliminary efficacy of the compound

Read the detailed description

The phase I dose escalations will be conducted utilizing the standard 3+3 dose escalation method. Pharmacokinetic (PK) data will be obtained for PBF-999.

The phase I dose expansion will consist of 1 group including immunotherapy naïve and pretreated (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations) solid tumors cancer patients. Pharmacodynamic (PD) data will be obtained for potential biomarker analysis with pre-treatment and on-treatment tumor biopsies.

Phase I Dose Escalation (3+3 Design):

  1. The MTD will be defined as the highest dose level at which less than 2 out of 6 patients (<33%) experience DLT in Cycle 1 (first 28 days).

Phase I Safety Expansion Once RP2D has been declared for PBF-999 using the standard 3+3 design, up to 20 additional solid tumor cancer patients may be treated at the RP2D to further explore safety and tolerability of the selected PBF-999 dose.

Patients in this study will be males or females 18 years of age or older. Patients must have histologically or cytologically confirmed cancer with at least one measurable lesion, with adequate organ and marrow function, and with ECOG performance status of 0-1. Eligible patients must have received at least one prior line of therapy for their disease.

Conditions
Cancer
Being tested
PBF-999
Keywords
solid tumors, PDE10 inhibitors, Immunoncology
Medical subject headings
Neoplasms

What participants receive

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

  • PBF-999Drug

    Phosphodiesterase 10 inhibitor (PDE10i)

Study groups in NCT03786484
Study groupRoleWhat they receive
PBF-999 20 mgExperimentalNot described
Receives: Drug: PBF-999
PBF-999 40 mgExperimentalNot described
Receives: Drug: PBF-999
PBF-999 80 mgExperimentalNot described
Receives: Drug: PBF-999
PBF-999 120 mgExperimentalNot described
Receives: Drug: PBF-999
recommended phase 2 dose (RP2D)ExperimentalNot described
Receives: Drug: PBF-999

What is being measured

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

  1. Number of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03

    AEs will be described by system organ class and preferred tem using the Medical Dictionary for Regulatory Activities (MedDRA). Clinically relevant Laboratory abnormalities with toxicity grades according to the NCI CTCAE v4.03 will be derived and summarized.

    Measured: 28 Days

  2. The Maximun Tolerated Dose (MTD) of PBF-999

    The MTD evaluation will be based on the Dose-limiting Toxicity (DLT) of the treated Population and will include Adverse events (AEs), Serious Adverse events (SAEs) and laboratory evaluations. DLT Evaluable Population will be all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with PBF-999 and complete the safety follow-up through the DLT evaluation period or experience a DLT during the DLT evaluation period.

    Measured: 28 Days

Secondary outcomes (9)

  1. Time to PBF-999 peak concentration in plasma "Tmax

    The parameter will be calculated from plasma samples collected at days 1, day 8 and 29 after drug administration. It will consist in the time (in minutes) to reach the maximum "PBF-1129" concentration in plasma samples of patients after oral administration of PBF-999.

    Measured: Day 1, Day 8 and Day 29

  2. PBF-999 peak concentration in plasma "Cmax"

    The parameter will be calculated from plasma samples collected at days 1, 8 and 29 after drug administration. It will consist in the maximum plasma concentration (ng/mL) of PBF-999 observed after administration.

    Measured: Day 1, Day 8 and Day 29

  3. The area under PBF-999 plasma concentration-time curve to infinite time "AUC(0-inf)

    The parameter will be calculated from plasma samples collected at days 1, 8 and 29 after drug administration. It will consist in the area under the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase. "AUC(0-inf)" will be given in Amount·time/ volume units

    Measured: Day 1, Day 8 and Day 29

  4. PBF-999 half-life in plasma " t½"

    The parameter will be calculated from plasma samples collected at days 1, 8 and 29 after drug administration. It will consist in the terminal half-life of PBF-999 in plasma. "t½" will be given in hours (h)

    Measured: Day 1, Day 8 and Day 29

  5. Efficacy of PBF-999 treatment as measured by Objective response rate (ORR

    ORR: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).ORR is defined as confirmed complete response (CR) or partial response (PR) based on modified RECIST v1.1.

    Measured: 2 years

  6. Efficacy of PBF-999 as measured by Disease control rate (DCR)

    The disease control rate (DCR) will be estimated considering the following variables: Complete response (CR), Partial response (PR) and stable disease (SD) as described by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). These variables will be assessed based on Imaging-based evaluation methods as chest x-ray, conventional computed tomography (CT) and magnetic resonance imaging (MRI) that will be performed every 2 cycles of 28 days administration.

    Measured: 2 years

  7. Efficacy of PBF-999 as measured by duration of response (DoR)

    Duration of response (DoR) is defined as the duration from the first documentation of OR to the first documented disease progression or death due to any cause, whichever occurs first

    Measured: 2 years

  8. Efficacy of PBF-999 as measured by progression-free survival (PFS)

    Progression-free survival (PFS) will be measured from the start of treatment until the documentation of disease progression or death due to any cause, whichever occurs first. For subjects who are alive and progression-free at the time of data cut-off for analysis, PFS will be censored at the last tumor assessment date.

    Measured: 2 years

  9. Efficacy of PBF-999 as measured by overall survival (OS)

    Overall survival (OS) will be determined as the time from the start of treatment until death due to any cause

    Measured: 2 years

Timeline

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

  1. First posted26 Dec 2018
  2. Study start1 Oct 2017
  3. Primary completion30 Jun 2022
  4. Study completion30 Jun 2022

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
Sequential
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03786484
Sponsor's protocol ID
VHIO-PBF-999-01
Status last verified
Jan 2022
First submitted
20 Dec 2018
Last updated
26 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PBF-999 in people with Cancer, run by Palobiofarma SL at 1 site in Spain.

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 8 inclusion and 9 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 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. 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?

Number of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03786484.

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 26 Jan 2023.

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