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LymphomaPhase 1NCT03229278

Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

A Phase 1 study testing Enzyme Inhibitor Therapy, Laboratory Biomarker Analysis and Nivolumab in people with Lymphoma and Metastatic Malignant Solid Neoplasm, run by Rutgers, The State University of New Jersey at 1 site in United States.

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

This phase I trial studies the best dose and side effects of trigriluzole in combination with nivolumab and pembrolizumab in treating patients with solid malignancies or lymphoma that has spread to other places in the body or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Enzyme Inhibitor Therapy, Laboratory Biomarker Analysis and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
3 Oct 2017to 30 Oct 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients must have histologically confirmed solid malignancy or lymphoma that is metastatic or unresectable
  • There is reasonable expectation of response to pembrolizumab or nivolumab, and one of the drugs is available from the commercial supply; this includes (but is not limited to) the following tumor types: melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, bladder cancer, and classic Hodgkin lymphoma
  • The patient must have failed at least one line of standard treatment, with the following exceptions in which a PD-1 antibody is Food and Drug Administration (FDA) approved in the first-line setting:
  • Melanoma patients
  • Non-small cell lung cancer patients without EGFR or ALK genomic tumor aberrations whose tumors have high PD-L1 expression (tumor proportion score [TPS] >= 50%) as determined by an FDA-approved test
  • Patients must give informed consent
Show all 15Show fewer
  • Prior chemotherapy, immunotherapy, radiotherapy or major surgery (including radiation therapy or surgery for treatment of brain metastases) must be completed at least 3 weeks before study entry; prior PD-1 or PD-L1 therapy is acceptable
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin > 8.0 mg/dL (without transfusion in the preceding 7 days)
  • Platelets >= 70,000 /uL
  • Total bilirubin within normal institutional limits (patients with Gilbert's syndrome must have a total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2 X institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 X institutional ULN
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm by computed tomography (CT) scan, positron emission tomography (PET)/CT scan, magnetic resonance imaging (MRI) or caliper/ruler measurement by clinical exam; lymph nodes: to be considered pathologically enlarged and measurable, a lymph node must be >= 15 mm in short axis when assessed by CT scan; lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy
  • Ability to swallow pills

Who cannot join

  • Systemic immunosuppressive medications such as steroids; the following steroid formulations are permitted: intranasal, intra-articular, and inhaled steroids
  • History of immune-related adverse event from prior immunotherapy treatment that has not improved to grade 0-1; subjects with grade 2 hypothyroidism and grade 2 adrenal insufficiency requiring continued medical treatment may enroll provided that they are asymptomatic and stable on their dose of hormone replacement
  • Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient?s ability to complete the study, at the discretion of the investigator, including active autoimmune disease requiring treatment within the past 30 days
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption)' physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
  • Second primary malignancy, except those second primary malignancies that are not considered to be competing causes of death in the opinion of the treating investigator; examples include: in situ carcinoma of the cervix, adequately treated non-melanoma carcinoma of the skin, or other malignancy treated at least 5 years previously with no evidence of recurrence
  • Patients with active, untreated central nervous system (CNS) metastases will be excluded from this clinical trial; patients who have brain metastases that been treated with radiation therapy or surgery will be required to have a washout period of at least 3 weeks prior to study entry, must be neurologically asymptomatic, and must not require systemic steroids
  • Women of child-bearing potential and men must agree to use adequate contraception prior to the start of treatment, for the duration of treatment, and for 5 months after last dose of study treatment
  • Patients with immune deficiency have impaired immune responses, therefore, known human immunodeficiency virus (HIV)-positive patients are excluded from the study

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

Official title: A Phase I Study to Evaluate the Safety of Trigriluzole (FC-4157/BHV-4157) in Combination With PD-1 Blocking Antibodies

This phase I trial studies the best dose and side effects of trigriluzole in combination with nivolumab and pembrolizumab in treating patients with solid malignancies or lymphoma that has spread to other places in the body or cannot be removed by surgery. Trigriluzole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab and pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving trigriluzole in combination with nivolumab and pembrolizumab may work better at treating patients with solid malignancies or lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. The primary objective of this study is to determine the safety of trigriluzole in combination with PD-1 inhibiting antibodies, and to define a maximum tolerated dose (MTD) of trigriluzole in combination therapy.

SECONDARY OBJECTIVES:

  1. To characterize the efficacy of the combination therapy. II. To identify markers of response to trigriluzole in the tumor microenvironment.

OUTLINE: This is a dose-escalation study of trigriluzole.

Patients receive trigriluzole orally (PO) every other day (QOD), twice daily (BID), every morning (QAM) or every bedtime (QHS) on days -14 to -1. Patients then receive nivolumab intravenously (IV) over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD, BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 3 years.

Being tested
Enzyme Inhibitor Therapy, Laboratory Biomarker Analysis, Nivolumab, Pembrolizumab
Medical subject headings
Lymphoma, Neoplasm Metastasis, Melanoma, Carcinoma, Renal Cell, Urinary Bladder Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • Enzyme Inhibitor TherapyDrug

    Given trigriluzole PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03229278
Study groupRoleWhat they receive
Treatment (trigriluzole, nivolumab, pembrolizumab)ExperimentalPatients receive trigriluzole PO QOD, BID, QAM or QHS on days -14 to -1. Patients then receive nivolumab IV over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD, BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Enzyme Inhibitor Therapy; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Pembrolizumab

What is being measured

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

  1. Maximum Tolerated Dose (MTD))/Recommended Phase 2 Dose of Trigriluzole

    The MTD of trigriluzole in combination with nivolumab will be identified. The MTD will then be tested in combination with pembrolizumab using the same escalate/de-escalate/stay rules. Data on the adverse event type, severity and frequency will be recorded.

    Measured: Four weeks

Secondary outcomes (10)
  1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)

    A DLT was any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) that was possibly Trigriluzole or Nivolumab related. CTCAE 3.0 Grade 3 is a severe AE and Grade 4 is a life- threatening or disabling AE. DLTs were collected to determine the Maximum-Tolerated Dose (MTD), which is defined as the dose level below the dose at which 33% of participants experienced a DLT.

    Measured: Four weeks

  2. Objective Response Rate Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 95% confidence intervals [CI]) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 95% CI).

    Measured: Up to 3 years

  3. Overall Survival

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to 3 years

  4. Time to Next Therapy or Death

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to 3 years

  5. Freedom From New Metastases

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to 3 years

  6. Landmark Survival Rates at 1 Year

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: 1 year

  7. Landmark Survival Rate at 2 Years

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: 2 years

  8. Duration of Response for Responding Patients

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to 3 years

  9. Progression Free Survival

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to 3 years

  10. Time to Treatment Failure

    Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to 3 years

Timeline

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

  1. First posted25 Jul 2017
  2. Study start3 Oct 2017
  3. Primary completion20 Oct 2022
  4. Study completion30 Oct 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03229278
Sponsor's protocol ID
051707
Other IDs
NCI-2017-01155, Pro20170000453, Pro20170000453, P30CA072720
Status last verified
Nov 2023
First submitted
18 Jul 2017
Last updated
6 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.

    PubMed 39462179
  • Silk AW, Saraiya B, Groisberg R, Chan N, Spencer K, Girda E, Shih W, Palmeri M, Saunders T, Berman RM, Coric V, Chen S, Zloza A, Vieth J, Mehnert JM, Malhotra J. A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors. Eur J Med Res. 2022 Jul 2;27(1):107. doi: 10.1186/s40001-022-00732-w.

    PubMed 35780243

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Enzyme Inhibitor Therapy, Laboratory Biomarker Analysis and Nivolumab in people with Lymphoma and Metastatic Malignant Solid Neoplasm, run by Rutgers, The State University of New Jersey at 1 site in United States.

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 15 inclusion and 8 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 6 Dec 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 United States. 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?

Yes. Results are posted in the registry (first posted 6 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dose (MTD))/Recommended Phase 2 Dose of Trigriluzole (time frame: Four weeks). 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 NCT03229278, which also lists 2 linked publications.

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 6 Dec 2023.

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