Safety Study of Pritumumab in Brain Cancer
- Conditions
- Malignant Primary Brain TumorsBrain Metastases, Adult
- Interventions
- Registration Number
- NCT04396717
- Lead Sponsor
- Nascent Biotech
- 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
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Pritumumab Pritumumab 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.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Up to 24 weeks 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
Name Time Method Intra-cranial Objective Response Rate 2 months Intra-cranial objective response rate at 2 months as assessed by the Response Assessment in Neuro-oncology (RANO) criteria
Trial Locations
- Locations (2)
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States