Clinical Trials /

Testing the Safety of CB-5339 in Patients With Cancer

NCT04372641

Description:

This phase I trial studies the side effects and best dose of CB-5339 in treating patients with solid tumors that has spread to other places in the body (advanced) or lymphomas. CB-5339 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Testing the Safety of CB-5339 in Patients With Cancer
  • Official Title: A Phase I Trial of the P97 Inhibitor CB-5339 in Patients With Advanced Solid Tumors and Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: NCI-2019-08664
  • SECONDARY ID: NCI-2019-08664
  • SECONDARY ID: 10349
  • SECONDARY ID: 10349
  • NCT ID: NCT04372641

Conditions

  • Aggressive Non-Hodgkin Lymphoma
  • Indolent Non-Hodgkin Lymphoma
  • Locally Advanced Malignant Solid Neoplasm
  • Metastatic Malignant Solid Neoplasm

Interventions

DrugSynonymsArms
p97 Inhibitor CB-5339 TosylateCB 5339 Tosylate, CB-5339 Tosylate, CB5339 TosylateTreatment (p97 inhibitor CB-5339 tosylate)

Purpose

This phase I trial studies the side effects and best dose of CB-5339 in treating patients with solid tumors that has spread to other places in the body (advanced) or lymphomas. CB-5339 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To establish the safety, tolerability, and recommended phase 2 dose (RP2D) of p97
      inhibitor CB-5339 tosylate (CB-5339) administered orally on a schedule of once daily, 4 days
      on and 3 days off, in patients with advanced solid tumors and lymphomas.

      SECONDARY OBJECTIVES:

      I. To evaluate the pharmacokinetic profiles of CB-5339. II. To assess the preliminary
      antitumor activity of CB-5339 in patients with advanced solid tumors and lymphomas.

      III. To determine the effects of CB-5339 on the ubiquitin proteasome system and on markers of
      cell death in pre- and post-treatment tumor biopsies and peripheral blood mononuclear cell
      (PBMC)s.

      EXPLORATORY OBJECTIVE:

      I. To evaluate potential associations between CB-5339 activity and genomic alterations
      assessed in circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

      OUTLINE: This is a dose-escalation study.

      Patients receive p97 inhibitor CB-5339 tosylate orally (PO) once daily (QD) 4 days on and 3
      days off. Cycles repeat every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (p97 inhibitor CB-5339 tosylate)ExperimentalPatients receive p97 inhibitor CB-5339 tosylate PO QD 4 days on and 3 days off. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • p97 Inhibitor CB-5339 Tosylate

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologically documented metastatic or locally advanced (not amenable
             to surgery) solid tumors whose disease has progressed on standard therapy or for which
             there is no available standard therapy or therapy known to prolong survival; or
             aggressive lymphoma who have refused or have no remaining curative options (e.g., stem
             cell transplant). Patients with indolent lymphomas must have undergone 3 or more prior
             regimens of therapy

          -  Any prior therapy must have been completed >= 4 weeks (6 weeks for nitrosoureas and
             mitomycin C) or, if known, >= 5 half-lives of the prior agent (whichever is shorter)
             prior to enrollment on protocol (minimum of 1 week between prior therapy and study
             enrollment), and the participant must have recovered to eligibility levels from prior
             toxicity. Prior definitive radiation should have been completed >= 4 weeks or
             palliative radiation should have been completed >= 2 weeks prior to study enrollment
             and all associated toxicities resolved to eligibility levels (patients on study may be
             eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy
             at the principal investigator [PI]'s discretion). Patients must be >= 2 weeks since
             any investigational agent administered as part of a phase 0 study (where a
             sub-therapeutic dose of drug is administered) at the PI's discretion and should have
             recovered to grade 1 or baseline from any toxicities

          -  Patients who have had prior monoclonal antibody therapy must have completed that
             therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to
             enrollment on protocol (minimum of 1 week between prior therapy and study enrollment)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
             and life expectancy > 3 months

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL (solid tumor patients)

          -  Platelets >= 75,000/mcL (lymphoma patients)

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 x institutional ULN

          -  Creatinine =< 1.5 x institutional ULN OR 60 mL/min/1.73 m^2 for patients with
             creatinine levels above 1.5 x institutional normal

          -  The effects of CB-5339 on the developing human fetus are unknown. For this reason and
             because p97 inhibitors agents may be teratogenic, women of child-bearing potential and
             men must agree to use adequate contraception (hormonal or barrier method of birth
             control; abstinence) prior to study entry and for the duration of study participation
             and for 4 months afterwards. Should a woman become pregnant or suspect she is pregnant
             while she or her partner is participating in this study, she should inform her
             treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of CB-5339 administration

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Subjects on the expansion cohort must also be willing to undergo two core biopsy
             procedures if there is a lesion amenable to biopsy

          -  Left ventricular ejection fraction >= the lower limit of normal by echocardiogram
             (ECHO) at entry

          -  Mean QT interval corrected for heart rate (QTc) < 470 ms using Fridericia's correction

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study

          -  Patients who have not recovered from adverse events due to prior anti-cancer therapy
             (i.e., have residual toxicities > grade 1) with the exception of alopecia

          -  Patients who are receiving any other investigational agents

          -  Patients with clinically significant illnesses which would compromise participation in
             the study, including but not limited to active or uncontrolled infection, immune
             deficiencies, hepatitis B, hepatitis C, active tuberculosis, uncontrolled asthma,
             symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac
             arrhythmia, myocardial infarction within the past 6 months, cerebral vascular
             accident/stroke within the past 6 months, or psychiatric illness/social situations
             that would limit compliance with study requirements.

               -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
                  therapy with undetectable viral load within 6 months are eligible for this trial.

               -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
                  viral load must be undetectable on suppressive therapy, if indicated

          -  Patients with known brain metastases or carcinomatous meningitis are excluded from
             this clinical trial, with the exception of patients whose brain metastatic disease
             status has remained stable for >= 4 weeks after treatment of the brain metastases.
             Patients on anti-seizure medications may be enrolled at the discretion of the
             principal investigator providing that these patients are taking non-enzyme- inducing
             anti-seizure medications or can be converted to these

          -  Pregnant women are excluded from this study because CB-5339 may have the potential for
             teratogenic or abortifacient effects. Because there is an unknown but potential risk
             for adverse events in nursing infants secondary to treatment of the mother with this
             agent, breastfeeding should be discontinued if the mother is treated with CB-5339

          -  Current or previous history of sight-threatening retinal disease, including (but not
             limited to) proliferative diabetic retinopathy, severe retinal vascular disease, and
             advanced age-related macular degeneration

          -  Patients with a history of QT-prolongation or of Torsades de pointes (TdP), or of
             taking QT-prolonging drugs, are not eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (Phase I)
Time Frame:30 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacodynamic analysis (expansion phase)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Response assessment
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

July 3, 2020