Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Vaccines

Polio vaccine booster will be administered 1 week prior to PVSRIPO injection. On the day of PVSRIPO injection (Day 0), a pre-treatment biopsy is obtained. PVSRIPO in injected into the tumor mass at a dose of 1x10\^8 TCID50. On day 14, women will undergo standard-of-care surgical resection of PVSRIPO-treated tumor.

The live, attenuated, oral (Sabin), serotype 1 poliovirus vaccine booster will be administered 1 week before PVSRIPO injection. The study drug, PVSRIPO, is the live attenuated, oral (Sabin) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site (IRES) derived from the human rhinovirus type 2 (HRV2). It will be given at a dose of 1x10\^8 TCID50 (tissue culture infectious dose) directly into the breast tumor.

PVSRIPO

Darell Bigner, MD, PhD

This is a pilot study to examine PVSRIPO bioactivity in tumor tissue after intratumoral administration of PVSRIPO in women with invasive breast cancer.

The study drug PVSRIPO is the live attenuated, oral (Sabin) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site (IRES) derived from the human rhinovirus type 2 (HRV2). The purpose of this pilot study is to examine PVSRIPO bioactivity in tumor tissue after intratumoral administration of PVSRIPO in women with invasive breast cancer. The hypothesis is that administration of PVSRIPO in the tumor causes inflammation, which stimulates innate and adaptive immune activation in invasive breast cancer. Enrollment target will include six women with invasive breast cancer. Women with stage II-IV invasive breast cancer with at least 1 cm of residual tumor after chemotherapy and scheduled for standard of care surgery will be eligible.

The objective of the study is to investigate PVSRIPO-mediated inflammation and immunity in women invasive breast cancer. The primary exploratory objective is to describe the change in the amount of tumor infiltrating immune cells in tumor tissue pre- and post-injection of PVSRIPO by H\&E (Haemotoxylin and Eosin).

Other exploratory objectives are: 1.) to examine tumor tissue pre- and post-injection of PVSRIPO for inflammatory and immune signature using arrays, CD155 expression by immunohistochemistry (IHC), immune cell infiltrate by IHC and tumor infiltrating immune cells using flow cytometry (post-injection only); and 2) To examine blood for inflammatory and immune signature using arrays, immune cell composition (antigen presenting cells, B cells and T cells), T cell activation by flow cytometry and B cell activation by ELISA and peptide arrays. Blood will be collected on day -7 (before polio vaccine booster), day 0 (before PVSRIPO injection), day 2 (after PVSRIPO), day 14 (after PVSRIPO before surgery), and in follow-up at months 1 and 6 post-PVSRIPO.

All subjects will receive intratumoral injection of the study drug PVSRIPO at a dose of 1x10\^8 TCID50 (tissue culture infectious dose). On Day 14 after injection, subjects will undergo standard-of-care surgical resection of PVSRIPO-treated tumor.

Examining Bioactivity of PVSRIPO in Invasive Breast Cancer

Examining Oncolytic Poliovirus Bioactivity in Tumor Tissue After Intratumoral Administration of PVSRIPO in Women With Invasive Breast Cancer

To describe the change in the amount of tumor infiltrating immune cells in tumor tissue pre- and post-injection of PVSRIPO

Duke University

United States Department of Defense

Istari Oncology, Inc.

All participants received a single lerapolturev dose

All Participants Treated

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

W. Garrett Nichols, MD MS

All participants received a single lerapolturev dose.

participants tumor tissue available pre- and post-treatment with PVSRIPO

Change in Tumor Infiltrating Immune Cells

Overall Study

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

A single dose of PVSRIPO into a single lesion.

A single dose of PVSRIPO into 2 different lesions, 21 days apart, when applicable per dose escalation guidelines.

A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines.

A single dose of PVSRIPO into a single lesion, followed by PVSRIPO injected into up to 6 lesions at Day 10 and every 21 days thereafter.

Georgia Beasley, MD

This study is a Phase I study of oncolytic polio/rhinovirus recombinant (PVSRIPO) to primarily characterize the safety and tolerability of PVSRIPO in patients with AJCC Stage IIIB, IIIC, or IV melanoma in a modified 3+3 phase 1 trial design. Lesion biopsies and blood samples will be obtained pre- and post-injection throughout the study for routine histology/molecular genetic testing and immunologic analysis, respectively. Exploratory objectives include describing the response rates of PVSRIPO-injected versus non-injected lesion(s), the number of CD8 positive T cells present in the tumor biopsies before and after injection of PVSRIPO, and after PVSRIPO administration: the pathologic response in tumor biopsies, changes in the tumor microenvironment, and how systemic immune cell populations may change.

The Primary Objective of the study is to determine the safety profile of PVSRIPO in Stage IIIB, IIIC, and IV recurrent melanoma patients as determined by DLTs by cohort, as well as in those retreated with PVSRIPO, when PVSRIPO is injected intralesionally into 1 to 3 or more cutaneous or subcutaneous lesions. As planned, up to 18 patients may be treated with PVSRIPO.

Biopsy material will be obtained from tumor tissue prior to and following virus administration, which may be subjected to routine histology along with molecular genetic testing and evaluation of pathological response. Whole blood for immunologic analyses will also be collected throughout the study period.

Routine study visits will occur through Day 126. Thereafter, visits will occur every 2-3 months for up to 2 years for subjects who do not progress. For patients with progressive disease, chart review only will occur every 3 months starting at the time of progression.

Patients who previously participated in Cohorts 0 through 3, who in the opinion of the investigator, may benefit from continued PVSRIPO administration, may be eligible to receive additional injections.

PVSRIPO for Patients With Unresectable Melanoma

A Phase I Trial of PVSRIPO for Patients With Unresectable Melanoma

To describe the response rates via lesion size of PVSRIPO-injected versus non-injected lesion(s).

To describe the number of CD8 positive T cells present in the tumor biopsies before and after injection of PVSRIPO.

Determine the pathologic response in tumor biopsies after PVSRIPO by confirming presence or absence of viable tumor cells.

Determine viral replication via a number of methods (e.g., qRT-PCR, ICH).

Determine changes in the tumor microenvironment from biopsies after PVSRIPO; includes but not limited to examination of CD8, PVR (CD155), PD-L1, CD4, FoxPE, and PD-1.

Describe how systemic immune cell populations may change after treatment with PVSRIPO.

To characterize the safety and tolerability of PVSRIPO in AJCC Stage IIIB, IIIC, or IV melanoma.

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

PVSRIPO (5x10\^7 TCID50) delivered intratumorally via convection enhanced delivery (CED).

This is an open-label, single-arm, non-randomized, intermediate-sized expanded access study evaluating the safety, efficacy, and tolerability of PVSRIPO delivered via intratumoral infusion, in subjects with glioblastoma (GBM) who are ineligible to participate in clinical study with PVSRIPO that is currently open to enrollment.

EAP for the Treatment of Glioblastoma With PVSRIPO

Expanded Access Protocol for the Treatment of Glioblastoma With PVSRIPO

Symptoms and General Pathology

Nervous System Diseases

Recurrence

Brain Neoplasms

Antineoplastic Agents

Antibodies

Atezolizumab

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Single PVSRIPO infusion at a dose of 5x10\^7 tissue culture infected dose (TCID50). Atezolizumab infusions at a dose of 1200 mg every three weeks for up to two years.

Darell D Bigner, MD, PhD

Dina M Randazzo, DO

This study evaluates the safety of PVSRIPO treatment in combination with Atezolizumab in patients with WHO grade IV malignant glioma. All patients will receive a single PVSRIPO infusion followed by atezolizumab infusions every three weeks for up to two years.

The purpose of this phase1b/2 study of atezolizumab in combination with oncolytic polio/rhinovirus recombinant (PVSRIPO) in patients with recurrent World Health Organization (WHO) grade IV malignant glioma is to assess the safety of the combination of PVSRIPO + atezolizumab, as well as describe the survival of patients receiving this novel therapy combination. Patients will receive an intratumoral infusion of PVSRIPO followed by atezolizumab treatment with possible surgical resection after the first atezolizumab treatment at the discretion of the treating neurosurgeon.

Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma

A Phase 1b/2 Trial of PVSRIPO in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma

Any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, or any life-threatening event, or treatment-related death.

Proportion of patients alive at 24 months after PVSRIPO infusion

Genentech, Inc.

Darell Bigner

Sponsor-Investigator

Nivolumab

Cohort 1 will include 15 patients who progressed within 3 months (primary resistance) of starting PD-1 therapy

Cohort 2 will include 15 patients who progressed after at least 3 months of PD-1 therapy

Georgia Beasley

In this study, patients with metastatic melanoma who have at least one injectable lesion that has been refractory to PD-1 therapy (n=30 patients) will be enrolled. Cohort 1 will include 15 patients who progressed within 3 months (primary resistance) of starting PD-1 therapy and cohort 2 will be patients who progressed after at least 3 months of PD-1 therapy. Patients will receive up to 7 injections of PVSRIPO intra-lesionally in combination with Nivolumab. Nivolumab will be administered according to the FDA-approved dosing schedule of 480 mg intravenously every 4 weeks, beginning \~10 days after the first PVSRIPO infusion and will continue for 4 cycles. Nivolumab may be continued up to 2 years per standard of care after the completion of the PVSRIPO injections.

Patients must have histologically proven unresectable melanoma, stage IIIB, IIIC, IIID, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body PET scan, and MRI of the brain within 4 weeks prior to administration of study drug). Patients must have failed PD-1 therapy as judged by the treating physician.

Patients will initially receive one injection of PVSRIPO intra-lesionally. Based on a phase 1 study of the agent in adult patients with recurrent GBM, the starting amount to be delivered will be 1x108 tissue culture infectious dose (TCID50) prior to initiation of nivolumab. Nivolumab will be administered according to the FDA-approved dosing schedule of 480 mg intravenously every 4 weeks, beginning \~10 days after the first PVSRIPO infusion and will continue for 4 cycles. PVSRIPO will then be given intralesionally to multiple lesions (if present) at days 38, 66, and 94.

At Day 108 after 4 doses of nivolumab and 4 treatments of PVSRIPO, imaging and a full disease assessment will be done and iRECIST determined. A patient with complete response (CR) or a partial response (PR) (at least at 75% decrease in the sum of all diameters of all target lesions plus new lesions) will continue on nivolumab for up to 2 years. For patients with PR (\< 75% decrease), stable disease (SD), or progressive disease (PD), an additional 3 treatments of PVSRIPO q4weeks can be given concurrently with 3 doses of monthly nivolumab. The lesions will be chosen at discretion of principal investigator (PI) and can be new lesions, previously injected lesions, or untreated lesions. At Day 234 (±7 days), (after 7 total PVSRIPO injections and 8 doses of nivolumab), patients with PD will be off study, any patient with CR, PR, SD can receive up to 2 years total of nivolumab. If a patient has no remaining injectable lesions at any point during the study, PVSRIPO will not be given, but patients can continue on nivolumab.

PVSRIPO in Combination With Nivolumab in Melanoma

A Phase IB Trial of PVSRIPO in Combination With Nivolumab in Patients With Recurrent PD-1 Refractory Melanoma

Toxicities will be measured based on the number of adverse events as measured by clinical exams.

Bristol-Myers Squibb

Edwin L. Jones, Jr. and Lucille Finch Jones Cancer Research Professor

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Lerapolturev (intratumoral) will be dosed by Convection Enhanced Delivery (CED), infused twice, 4 days apart, in the remaining disease of recurrent Glioblastoma (rGBM) subjects following maximal safe resection of the disease recurrence.

To assess treatment response and/or immunologic responses in the brain, a tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, in the event that changes suggestive of tumor progression are seen on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED.

.

Lerapolturev (intratumoral) will be given by Convection Enhanced Delivery (CED), infused twice, 4 days apart, in the remaining disease of recurrent Glioblastoma (rGBM) subjects following maximal safe resection of their disease recurrence. This will be followed by subcutaneous injections of lerapolturev in the cervical perilymphatic (CPL) area on the same side as their tumor, weekly for 4 weeks and afterward every 3 weeks for about a year.

Following maximal safe resection of their tumor recurrence subjects will receive Lomustine as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Lerapolturev (intratumoral) will be dosed at 2x108 TCID50 in 3.0 mL x 2 doses (total dose 4x108 TCID50) by Convection Enhanced Delivery.

For the patients randomized to the lerapolturev Arm 1 of Stage 2, seven days (±2 days) following completion of the 2nd intratumoral infusion of lerapolturev, patients will begin cervical perilymphatic subcutaneous injection of lerapolturev at a dose of 2 x 108 TCID50 (in 0.5 ml diluent) around the cervical lymph node chain ipsilateral to the intracranial tumor.

Lerapolturev

Lomustine will be given as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Lomustine Pill

Madison Shoaf, MD

Stevie Threatt

The purpose of this research study is to determine the safety and efficacy of administering two doses of lerapolturev in residual disease (within tumor margins) after surgery, followed later by repeated injections of lerapolturev in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adult patients diagnosed with recurrent glioblastoma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

The study will be conducted in two stages: Approximately twelve patients with recurrent supratentorial glioblastoma will enroll in stage 1.

Stage 1 is a safety lead-in which will assess the safety of lerapolturev when infused twice, 4 days apart, via Convection Enhanced Delivery (CED) in the residual disease of recurrent Glioblastoma (GBM) patients following maximal safe resection of the enhancing/necrotic portion of the disease recurrence.

A tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, if imaging changes suggest tumor progression vs. immune effect on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED.

Stage 2 is a Phase 2 randomized clinical trial to compare the efficacy and safety of two treatment regimens for recurrent GBM patients who undergo maximal safe resection for their recurrence. Approximately eighty patients with recurrent supratentorial glioblastoma will enroll in stage 2 of the study.

Stage 2 has 2 arms and is randomized, like the flip of a coin. Arm 1 is Lerapolturev and Arm 2 is Lomustine. After the recurrent tumor has been removed by surgery, subjects will be randomly assigned to receive either the FDA-approved chemotherapy (lomustine) or the study drug (lerapolturev). Subjects receive lerapolturev infused in the residual disease via CED twice, 4-day apart. About 1 week after the 2nd lerapolturev infusion, subjects will start subcutaneous (under the skin) injections of lerapolturev into the area of the cervical lymph nodes (head and neck) nearest to their tumor weekly for 4 weeks and afterward every 3 weeks for about a year.

Subjects assigned to receive lomustine will begin taking it 3-4 weeks after surgery to remove their recurrent tumor. One prescribed dose of lomustine will be taken no more than once every 6 weeks, for no more than 1 year or up to 9 cycles.

Subjects will be followed for serious adverse events (side effects) for 30 days after stopping the study. Subjects' medical records will be reviewed for the remainder of their life, in order to collect data on subsequent treatments, disease progression, tumor size/volume, and survival.

There are risks to the study drug, lerapolturev, and the chemotherapy drug, lomustine. The most common risks of lerapolturev are headache, seizure, weakness on one side of the body, difficulty thinking or processing, difficulty receiving or responding to sensory information, fatigue, and difficulty speaking or comprehending. Risks associated with infusion procedure include mild discomfort at the infusion site, bleeding in the brain, pain, infection, and swelling of the brain. The study drug and procedures used together could also potentially cause more serious side effects. The most common risks of lomustine are changes in your red blood cell count, changes in platelets, changes in your liver, feeling confused and tired, poor appetite, and loss of ability to conceive or father a child.

Lerapolturev (PVSRIPO) in GBM

Randomized Phase 2 Clinical Trial of Repeated Intratumoral and Cervical Perilymphatic Lerapolturev Injections Versus Lomustine in Recurrent Glioblastoma (GBM)

Dose-limiting toxicities (DLTs) are defined as any of the following events that are possibly, probably, or definitely attributable to study treatment (i.e., lerapolturev) during dose escalation (Stage 1):

* Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms
* Any life-threatening event within 2 weeks
* Treatment-related death at least possibly, probably, or definitely attributable to study treatment
* Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion

Unacceptable toxicity is defined as any of the following events that are possibly, probably, or definitely attributable to study treatment:

* Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms
* Any life-threatening event within 2 weeks
* Treatment-related death at least possibly, probably, or definitely attributable to study treatment
* Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion

Median OS, where OS is defined as the time between randomization and death

Median PFS, where PFS is defined as the time between randomization and initial failure (disease progression or death)

Professor of Neurosurgery

Infections

Poliomyelitis

A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)

Dina Randazzo, DO

This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma.

This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of this study is to investigate the safety and efficacy (anti-tumor response and survival) of PVSRIPO in recurrent WHO grade IV malignant glioma.

Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment with PVSRIPO is allowed, provided retreatment eligibility criteria are met.

All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.

PVSRIPO in Recurrent Malignant Glioma

A Multicenter Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in Recurrent WHO Grade IV Malignant Glioma Patients

Assess objective anti-tumor response based on iRANO criteria.

Assess time of confirmed response to confirmed progressive disease/death.

Overall Survival, relative to external control group(s)

Overall survival at 24 and 36 months and greater

The percentage of patients classified as non-progressive by radiographic response based on standard criteria.

Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Examining Bioactivity of PVSRIPO in Invasive Breast Cancer	NCT03564782	Invasive Breast...	PVSRIPO	18 Years -	Istari Oncology, Inc.
PVSRIPO for Patients With Unresectable Melanoma	NCT03712358	Melanoma	PVSRIPO	18 Years -	Istari Oncology, Inc.
PVSRIPO for Patients With Unresectable Melanoma	NCT03712358	Melanoma	PVSRIPO	18 Years -	Istari Oncology, Inc.
EAP for the Treatment of Glioblastoma With PVSRIPO	NCT04599647	Glioblastoma	PVSRIPO	18 Years -	Istari Oncology, Inc.
Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma	NCT03973879	Malignant Gliom...	PVSRIPO Atezolizumab	18 Years -	Duke University
PVSRIPO in Combination With Nivolumab in Melanoma	NCT04125719	Melanoma	PVSRIPO Nivolumab	18 Years -	Duke University
Lerapolturev (PVSRIPO) in GBM	NCT06177964	Recurrent Supra...	Lerapolturev Lomustine Pill	18 Years -	Duke University
PVSRIPO in Recurrent Malignant Glioma	NCT02986178	Malignant Gliom...	PVSRIPO	18 Years -	Istari Oncology, Inc.

Spots Global Cancer Trial Database for pvsripo

Every month we try and update this database with for pvsripo cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pvsripo

Every month we try and update this database with for pvsripo cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pvsripo cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.