Clinical Trials /

Safety Study of Pritumumab in Brain Cancer

NCT04396717

Description:

Pritumumab is a human IgG1 kappa antibody that binds to a malignant tumor associated antigen, ecto domain-vimentin (EDV) which is expressed in a variety of tumor cells. Pritumumab was shown to have relatively high reactivity with brain cancer cell lines, while no reactivity was demonstrated with normal neurons, astrocytes or fetal cerebral cells. Pritumumab has notable antibody-dependent cellular cytotoxicity (ADCC), brain tumor penetration and antitumor activity in nude mouse human xenograft models. Primary Objectives - To determine the safety and/or tolerability and the recommended Phase 2 dose (RP2D) of escalating, intravenously (IV) administered Pritumumab doses in patients with recurrent gliomas or with brain metastases. Secondary Objectives - To determine pharmacokinetics and pharmacodynamics of Pritumumab - To identify preliminary signals of anti-tumor response to Pritumumab - To explore disease-related, patient-reported outcomes

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligoastrocytoma
  • Anaplastic Oligodendroglioma
  • Chordoma
  • Craniopharyngioma
  • Glioblastoma
  • Low Grade Glioma
  • Medulloblastoma
  • Meningioma
  • Pituitary Gland Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of Pritumumab in Brain Cancer
  • Official Title: A Phase 1, Sequential Cohort, Open-Label, Dose-Escalation Study of the Safety and CNS Exposure of Pritumumab in Patients With Brain Cancer

Clinical Trial IDs

  • ORG STUDY ID: 08091967
  • NCT ID: NCT04396717

Conditions

  • Malignant Primary Brain Tumors
  • Brain Metastases, Adult

Interventions

DrugSynonymsArms
PritumumabPritumumab

Purpose

Pritumumab is a human IgG1 kappa antibody that binds to a malignant tumor associated antigen, ecto domain-vimentin (EDV) which is expressed in a variety of tumor cells. Pritumumab was shown to have relatively high reactivity with brain cancer cell lines, while no reactivity was demonstrated with normal neurons, astrocytes or fetal cerebral cells. Pritumumab has notable antibody-dependent cellular cytotoxicity (ADCC), brain tumor penetration and antitumor activity in nude mouse human xenograft models. Primary Objectives - To determine the safety and/or tolerability and the recommended Phase 2 dose (RP2D) of escalating, intravenously (IV) administered Pritumumab doses in patients with recurrent gliomas or with brain metastases. Secondary Objectives - To determine pharmacokinetics and pharmacodynamics of Pritumumab - To identify preliminary signals of anti-tumor response to Pritumumab - To explore disease-related, patient-reported outcomes

Detailed Description

      This is an open-label, Phase 1, outpatient, dose escalation study of Pritumumab in patients
      with brain cancer who have failed prior therapy and have no other available options. In the
      first part of the study, escalating doses of Pritumumab of 1.6, 4.8, 8.0, 12.0, and 16.2
      mg/kg will be administered in a sequential, safety-driven manner to eligible patients
      according to standard 3+3 scheme, as an 1-hour IV infusion on Days 1, 8, 15, and 22 of each
      28-day treatment cycle. The dose levels may be modified upon obtained results. Once the
      maximum tolerated dose (MTD) is determined, an expansion cohort including 6-12 patients in
      selected tumor type at a dose equal or below to MTD is planned to determine the recommended
      Phase 2 dose (RP2D). A total of 42 patients may be administered with Pritumumab in this
      study.

      Patients will be treated with Pritumumab for a maximum of 6 cycles or until cancer
      progression or unacceptable toxicity. Patients will be followed after treatment completion
      every four months or until death or lost to follow-up. Standard clinical, laboratory and
      functional assessments will be employed to monitor for safety, tolerability and tumor
      response, including blood sampling for clinical biochemistries, pharmacokinetics, CSF and
      tissue samples, at frequency specified by the protocol. Patient-reported outcomes will also
      be assessed.
    

Trial Arms

NameTypeDescriptionInterventions
PritumumabExperimentalDose Escalation phase (3+3 patients): Pritumumab administered sequentially as 1-hour IV infusion, on Day 1, 8, and 22 of each 28-day treatment cycle at: 1.6 mg/kg, 4.8 mg/kg, 8.0 mg/kg, 12.0 mg/kg, and 16.2 mg/kg, for a maximum of 6 cycles or progression or unacceptable toxicity. Expansion phase (6-12 patients): Pritumumab administered as 1-hour IV infusion, on Day 1, 8, and 22 of each 28-day treatment cycle at or below MTD for a maximum of 6 cycles or progression or unacceptable toxicity.
  • Pritumumab

Eligibility Criteria

        Inclusion Criteria Subjects must meet all of the inclusion criteria to participate in this
        study.

          1. Ability to understand and the willingness to provide informed consent.

          2. Diagnosis

             Histologically confirmed diagnosis of brain cancer:

               -  glioblastoma (GBM),

               -  anaplastic astrocytoma (AA),

               -  anaplastic oligodendroglioma (AO),

               -  anaplastic mixed oligoastrocytoma (AMO),

               -  low grade gliomas,

               -  brain metastases,

               -  meningiomas, chordomas, medulloblastoma, craniopharyngiomas, pituitary tumors or

               -  leptomeningeal metastases

          3. Prior Therapy Has failed prior standard therapy including maximal safe surgical
             resection, radiation therapy (when appropriate for the specific cancer type), or
             systemic therapy or is intolerant of, or has refused other available therapies, but is
             still in need of therapy. No patients may receive Pritumumab prior to any surgery for
             their cerebral tumor

          4. Progression/Recurrence Has progression of brain cancer and measurable disease by
             magnetic resonance imaging (MRI) or computed tomography (CT) scan.

             For leptomeningeal metastases, positive cytology is acceptable if imaging is not
             measurable.

          5. Age Age ≥ 18 years.

          6. Performance Status Karnofsky Performance Status ≥ 60% (see Appendix A). Subjects must
             have a life expectancy of equal to or greater than 8 weeks.

          7. Organ and Marrow Function Requirements

             Hematology:

               -  Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

               -  Platelet count ≥ 100 x 109/L

               -  Hemoglobin ≥ 9.0 g/dL

               -  White blood cell (WBC) count ≥ 3.0 x 109/L

             Biochemistry:

               -  AST/SGOT and ALT/SGPT ≤ 5 x institution's ULN

               -  Total bilirubin ≤ 3 x institution's ULN

               -  Serum creatinine ≤ 2 x institution's ULN or 24-hour creatinine clearance ≥ 50
                  mL/min

               -  Alkaline phosphatase (ALP) ≤ 3 x ULN unless considered tumor related

               -  Estimated GFR > 50 mL/min

             Coagulation:

               -  INR ≤ 1.4

               -  PT/aPTT ≤ 1.2 x institution's ULN

          8. Contraception All fertile females and any man with a partner of child-bearing
             potential agrees to use adequate contraception which will include two of the
             following: hormonal or barrier method of birth control, or abstinence prior to study
             entry, for the duration of study participation, and for 30 days following completion
             of therapy.

          9. Although Pritumumab shows notable immunohistologic reactivity against active
             endometrial tissues, fertile female patients will be included in this study.

        Exclusion Criteria Subjects meeting any of the exclusion criteria at baseline will be
        excluded from study participation.

          1. Current or anticipated use of other investigational agents.

          2. Insufficient time for recovery from prior therapy:

               -  less than 28 days from any prior cytotoxic investigational agent,

               -  less than 14 days from any prior non-cytotoxic investigational agent,

               -  less than 28 days from prior cytotoxic therapy (except 23 days from prior
                  temozolomide at 5 day regimen and 14 days from prior temozolomide at daily
                  regimen, 14 days from vincristine, 42 days from nitrosoureas, 21 days from
                  procarbazine administration),

               -  less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen,
                  thalidomide, cis-retinoic acid, targeted therapies (radiosensitizer does not
                  count),

               -  less than 7 days for immunotherapy agents, e.g., DCVax, Celldex, PD1, etc.

          3. Less than 3 weeks from surgery or insufficient recovery from surgical-related trauma
             or wound healing.

          4. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Pritumumab plus any patently atopic patients who have a history of
             having experienced an episode of allergic anaphylaxis.

          5. Severe or uncontrolled medical disorder that would, in the investigator's opinion,
             impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal
             disease, chronic pulmonary disease or active, uncontrolled infection).

          6. Known diagnosis of human immunodeficiency virus (HIV) infection.

          7. Impaired cardiac function including any of the following:

               -  Congenital long QT syndrome or a known family history of long QT syndrome;

               -  History or presence of clinically significant ventricular or atrial
                  tachyarrhythmias

               -  Clinically significant resting bradycardia (< 50 beats per minute)

               -  Inability to monitor the QT interval by ECG

               -  QTc > 450 msec on baseline ECG. If QTc > 450 and electrolytes are not within
                  normal ranges, electrolytes should be corrected and then the patient re-screened
                  for QTc

               -  Myocardial infarction within 1 year of starting study drug

               -  Other clinically significant heart disease (e.g., unstable angina, congestive
                  heart failure, or uncontrolled hypertension)

          8. Any female patients who develop serious uterine hemorrhage during this study may need
             to be excluded from further treatment with Pritumumab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:Up to 24 weeks
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v.5.0 during first 24 weeks of treatment

Secondary Outcome Measures

Measure:Intra-cranial Objective Response Rate
Time Frame:2 months
Safety Issue:
Description:Intra-cranial objective response rate at 2 months as assessed by the Response Assessment in Neuro-oncology (RANO) criteria

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nascent Biotech

Last Updated

March 22, 2021