PVSRIPO With/Without Lomustine

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 62
• Participant gender: Both

Summary

This is a randomized phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) alone or in combination with the chemotherapy drug lomustine in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Darell D. Bigner, MD, PhD
• Treatments: Lomustine
• Last Updated: 2016-12-06

Criteria

Inclusion Criteria:

• Patients must have a recurrent supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (≥ 1 cm and ≤ 5.5 cm of contrast-enhancing tumor). Prior histopathology consistent with a World Health Organization (WHO) grade IV malignant glioma confirmed by the study pathologist

• Age ≥ 18 years of age at the time of entry into the study.

• Karnofsky Performance Score (KPS) ≥ 70%

• Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy

• Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy

• Neutrophil count ≥ 1000 prior to biopsy

• Hemoglobin ≥ 9 prior to biopsy

• Platelet count ≥ 125,000/µl prior to biopsy; Platelet count ≥ 100,000/µl prior to infusion

• Creatinine ≤ 1.2 x normal range prior to biopsy

• Positive serum anti-poliovirus titer prior to biopsy

• The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week prior to administration of the study agent.

• At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.

• A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study.

• Able to undergo brain MRI with and without contrast

Exclusion Criteria:

• Females who are pregnant or breast-feeding. Adults of reproductive potential not employing an effective method of birth control. Sexually active women of child bearing potential, whose partner is male, must use medically accepted birth control. Sexually active men, whose partner is a female of child bearing potential, must use a medically accepted birth control.

• Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate

• Patients with severe, active co-morbidity, defined as follow:

• Patients with an active infection requiring treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)

• Patients with known immunosuppressive disease or known human immunodeficiency virus infection

• Patients with known active Hepatitis B (HBV) or Hepatitis C (HCV) infection

• Patients with impaired cardiac function or clinically significant cardiac disease, such as congestive heart failure requiring treatment (New York Heart Association Class ≥ 2), uncontrolled hypertension or clinically significant arrhythmia; QTcF > 470 msec on electrocardiogram (ECG) if performed or congenital long QT syndrome; acute myocardial infarction or unstable angina pectoris < 3 months prior to study

• Patients with known lung (FEV1 < 50%) disease or uncontrolled diabetes mellitus

• Patients with albumin allergy

• Patients with gadolinium allergy

• Patients with a previous history of neurological complications due to poliovirus infection

• Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used.

• Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)] prior to starting the study drug unless patients have recovered from side effects of such therapy

• Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy.

• Patients may not be less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation

• Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy)

• If the MGMT (O(6)-methylguanine-DNA methyltransferase) promoter in their tumor is unmethylated, patients are not mandated to have received chemotherapy prior to participating in this trial.

• If the MGMT promoter in their tumor is methylated, patients must have received at least one chemotherapy regimen prior to participating in this trial.

• Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord, radiological evidence of active (growing) multifocal disease, subependymal or leptomeningeal disease

• Patients with undetectable anti-tetanus toxoid IgG (Immunoglobulin G)

• Patients with known history of agammaglobulinemia

• Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for PVSRIPO infusion

• Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)

• Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin

• Patients with a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine