Safety Study of Pritumumab in Brain Cancer

NCT04396717 | Completed Phase 1 FDA Drug

• 1 other identifier: 08091967
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Malignant Primary Brain Tumors; Brain Metastases, Adult

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v.5.0 during first 24 weeks of treatment

  Up to 24 weeks

Secondary Outcomes (1)

• Intra-cranial Objective Response Rate

  2 months

Study Arms (1)

Pritumumab

EXPERIMENTAL

Dose 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.

Biological: Pritumumab

Interventions

Pritumumab BIOLOGICAL

Pritumumab IgG1 human monoclonal antibody

Pritumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to provide informed consent.
• 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
• 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
• 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.
• Age Age ≥ 18 years.

You may not qualify if:

• Current or anticipated use of other investigational agents.
• 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.
• Less than 3 weeks from surgery or insufficient recovery from surgical-related trauma or wound healing.
• 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.
• 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).
• Known diagnosis of human immunodeficiency virus (HIV) infection.
• 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)

Sponsors & Collaborators

• Nascent Biotech: lead
• Hoag Memorial Hospital Presbyterian: collaborator

Study Sites (2)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Jose A. Carrillo, MD

  One Hoag Drive Newport Beach, CA 92663, United States

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, non-randomized, 3+3 dose escalation to determine MTD, followed by exoansion to 6-12 patients to determine RP2D. Subjects will continue study treatment until progressive disease or unacceptable toxicity. Follow-up will occur until death or lost to follow-up.

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: May 21, 2020
• Study Start: February 22, 2021
• Primary Completion: January 6, 2023
• Study Completion: January 6, 2023
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)