Clinical Trials /

Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma

NCT03556228

Description:

This is a multicenter, open-label, Phase 1 study of orally administered VMD-928 in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists

Related Conditions:
  • Breast Carcinoma
  • Lymphoma
  • Malignant Solid Tumor
  • Pancreatic Carcinoma
  • Thymic Carcinoma
  • Thymoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma
  • Official Title: An Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of VMD-928 in Subjects With Solid Tumors or Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: VMO-01C
  • NCT ID: NCT03556228

Conditions

  • Solid Tumor
  • Lymphoma

Interventions

DrugSynonymsArms
VMD-928 300-mg CapsulesVMD-928 300 mg

Purpose

This is a multicenter, open-label, Phase 1 study of orally administered VMD-928 in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists

Trial Arms

NameTypeDescriptionInterventions
VMD-928 300 mgExperimentalVMD-928 300-mg Capsules
  • VMD-928 300-mg Capsules

Eligibility Criteria

        Part-1 Escalation Phase [Key Inclusion]:

          -  Histologically or cytologically confirmed diagnosis of solid tumor malignancy or
             lymphoma that is not responsive to standard therapies, are unfit for standard
             chemotherapy or for which there is no approved or curative therapy.

          -  ECOG score of 0 or 1.

          -  Able to swallow and retain oral medication.

          -  Adequate organ system function.

        Part-2 Expansion Phase [Key Inclusion]:

          -  Part-1 Escalation Phase inclusion criteria.

          -  (a) Thymic carcinoma, thymoma, pancreatic cancer, or breast cancer (TNBC); or (b) any
             other cancer with histologically or cytologically or genomically confirmed diagnosis
             of NTRK1 (TrkA) mutation, or fusion, or overexpression, translocation, amplification
             or other alterations that may interfere with TrkA (NTRK1) signaling, as previously
             identified with prior testing as routinely performed at Clinical Laboratory
             Improvement Amendments (CLIA)-certified or other similarly-certified laboratories.

        Part-3 Pharmacodynamic Activity (Eligible subjects in Part-2 may enroll in Part-3):

          -  Part-2 Expansion Phase inclusion criteria.

          -  Tumor with readily accessible lesion that is amenable to biopsy and consent to pre-and
             post-dose biopsy.

        Key Exclusion Criteria (Part-1, -2 and -3):

          1. Received chemotherapy having delayed toxicity within the last 21 days (six weeks for
             prior nitrosourea or mitomycin C).

          2. Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or
             tumor embolization within the past 2 weeks.

          3. Received an investigational anti-cancer drug within 21 days or 5 half-lives of the
             investigational agent prior, whichever is shorter, to the first dose of VMD-928.

          4. Unresolved toxicity from previous anti-cancer therapy ≥ CTCAE Grade 1 (except alopecia
             or anemia) unless agreed to by both the Investigator and Sponsor.

          5. Known active infections including HIV disease.

          6. Currently pregnant, nursing, or planning to become pregnant during the course of the
             study.

          7. QTcF interval ≥ 480 msec.

          8. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA)
             functional classification system.

          9. Acute coronary syndromes (including unstable angina), coronary angioplasty, or
             stenting within the past 24 weeks.

         10. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would
             compromise the patient's safety or interfere with assessment of the drug.

         11. Psychological, familial, sociological, geographical or other concurrent conditions
             that would interfere with safety evaluation, limit the subject's ability to follow the
             procedures in the protocol or otherwise jeopardize compliance with the protocol.
             Subjects with uncontrolled major depression, bipolar disorder, or severe anxiety
             disorder are excluded.

             Key Exclusion Criteria (For Part-1 Escalation Phase only):

         12. Any current medical condition that would alter the absorption, distribution,
             metabolism or excretion of VMD-928 including but not limited to:

               -  Severe uncontrolled nausea or vomiting

               -  Severe uncontrolled diarrhea The intended population for VMD-928 are expected to
                  have had bowel resections and these subjects will be eligible for Part-1 Dose
                  Escalation phase.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number and severity of treatment-emergent AEs
Time Frame:Within two months of the first VMD-928 dose for each patient
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) of VMD-928.
Time Frame:Two to three months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Peak plasma concentration (Cmax) of VMD-928.
Time Frame:Two to three months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Incidence of Dose Limiting Toxicities.
Time Frame:Within two months of the first VMD-928 dose for each patient
Safety Issue:
Description:
Measure:Analgesic response as defined by the Brief Pain Inventory (BPI).
Time Frame:Within two months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Change in p-TrkA protein expression.
Time Frame:Pre-dose and within two months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between clinical antitumor and AUC.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between clinical antitumor and p-TrkA inhibition.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between analgesic response and p-TrkA inhibition.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between analgesic response and AUC.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:VM Oncology, LLC

Trial Keywords

  • TrkA
  • NTRK1
  • Thymic
  • Pancreatic
  • TNBC

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