Neoplasms

All Conditions

Nervous System Diseases

Infections

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Adenoviridae Infections

Oligodendroglioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

BIRC5 protein, human

Patients with unresectable tumors will undergo a biopsy followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.

The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Neural stem cells loaded with an oncolytic adenovirus

Maciej S Lesniak, MD

Malignant gliomas have a very poor prognosis with median survival measured in months rather than years. It is a disease in great need of novel therapeutic approaches. Based on the encouraging results of our preclinical studies which demonstrate improved efficacy without added toxicity, the paradigm of delivering a novel oncolytic adenovirus via a neural stem cell line in combination with radiation and chemotherapy is well-suited for evaluation in newly diagnosed malignant gliomas. The standard-of-care allows application of virotherapy as neoadjuvant therapy and assessment of the cooperative effects with radiation/chemotherapy without altering the standard treatment.

This is an open-label, phase 1, dose escalation trial that followed a 3x3 design. Three doses will be evaluated in the resectable cohorts: Cohort 1: 0.5x10\^8 NSCs loading 6.25x10\^10 vp; Cohort 2: 1.0x10\^8 NSCs loading 1.25x10\^11 vp; and Cohort 3: 1.5x10\^8 NSCs loading 1.875x10\^11 vp. Subjects enrolled have newly diagnosed high-grade glioma based on clinical and radiologic criteria; pathology will be confirmed at the time of surgical resection. Direct intra-tumoral injection of study product (NSC-CRAd-S-p7) will be done after resection but prior to closure. Subjects will then receive concomitant radiotherapy (RT) at a dose of 60Gy and chemotherapy with temozolomide (TMZ), 75 mg/m2, daily during RT. This will be followed by adjuvant TMZ dosed at 200 mg/m2 for 6 cycles. Subjects will be followed until disease progression with serial brain MRIs, and for survival up to 5 years. The non-resectable cohort will not opened due to limited product availability.

A Phase I study of neural stem cell based virotherapy in combination with standard radiation and chemotherapy for patients with newly diagnosed malignant glioma

Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma

Neural Stem Cell Oncolytic Adenoviral Virotherapy of Newly Diagnosed Malignant Glioma

Using a 3+3 dose escalation design, three to six patients were to be enrolled per dose in each of the 3 cohorts. If no patients in the cohort experienced a dose-limiting toxicity (DLT), then the next cohort enrolled a minimum of 3 patients. If one of three patients experienced a DLT, then 3 more patients were evaluated at that dose level. If none of these three additional patients experienced a DLT, then dose escalation occurs, unless this is the highest dose, in which case dose escalation is stopped and the highest dose is declared the MTD. If 1 or more of these additional 3 patients had a DLT, then three additional patients may be entered, after discussion with the sponsor, at the next lowest does level if only three patients were treated previously at that dose. If two or more patients experienced a DLT Dose escalation will be stopped; 3 more patients could be added with sponsor approval at the next lower dose level.

Per Response Assessment in Neuro-Oncology Criteria (RANO, 2017) for target lesions as assessed by MRI: Complete Response (CR): The enhancing tumor is no longer seen by neuroimaging; Partial Response (PR): Decrease of ≥ 50% in the product of two diameters with the patient on a stable or decreasing dose of steroids; Minor Response (MR): Decrease in diameter products of \< 50% with the patient on a stable or decreasing dose of steroids; Stable Disease (SD): The scan shows no change. Patients should be receiving stable or decreasing doses of steroids; Progression (P): Increase of \> 25% in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. A concomitant decrease in steroid dose will rule out a progression designation during the first two months after completion of radiation; Pseudoprogression (PP): Radiological changes without concomitant neurological changes.

National Cancer Institute (NCI)

Northwestern University

Professor and Chairman

Number of patients in each cohort affected by serious adverse events

Patients with resectable tumors underwent surgical resection followed by injection of neural stem cells loaded with the virus (0.5x10\^8 NSCs loading 6.25x10\^10 vp) and then received standard chemoradiotherapy.

Resectable Disease Cohort 1

Patients with resectable tumors underwent surgical resection followed by injection of neural stem cells loaded with the virus (.0x10\^8 NSCs loading 1.25x10\^11 vp) and then received standard chemoradiotherapy.

Resectable Disease Cohort 2

Patients with resectable tumors underwent surgical resection followed by injection of neural stem cells loaded with the virus (1.5x10\^8 NSCs loading 1.875x10\^11 vp) and then received standard chemoradiotherapy.

Resectable Disease Cohort 3

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus at dose level 0.5x10\^8 NSCs loading 6.25x10\^10 vp and then receive standard chemoradiotherapy.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Arm B: Resectable Disease Cohort 1

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus at dose level 1.0x10\^8 NSCs loading 1.25x10\^11 vp and then receive standard chemoradiotherapy.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Arm B: Resectable Disease Cohort 2

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus at dose level 1.5x10\^8 NSCs loading 1.875x10\^11 vp and then receive standard chemoradiotherapy.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Arm B: Resectable Disease Cohort 3

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Christina Amidei, PhD

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus (dose: 0.5x10\^8/NSCs/6.25x10\^10 vp) and then receive standard chemoradiotherapy. No dose limiting toxicities were experienced in this cohort.

Arm B/Cohort 1

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus (dose: 1.0x10\^8 NSCs/1.25x10\^10 vp) and then receive standard chemoradiotherapy. No dose limiting toxicities were experienced in this cohort.

Arm B/Cohort 2

.5x10\^8 NSCs/1.875x10\^10 vp

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus (dose: 1.5x10\^8 NSCs/1.875x10\^10 vp) and then receive standard chemoradiotherapy. One dose limiting toxicity event was experienced in this cohort, prompting 3 additional patients being added to the cohort; no dose limiting toxicities were experienced in this addition to the cohort, and this dose was determined to be the MTD.

ArmB/Cohort 3

No screen failures were encountered and all 12 patients were evaluable.

Percentage of Dose-limiting Toxicities

Percentage of participants with tumor response: Partial

Percentage of participants with tumor response: Pseudoprogression

Percentage of participants with tumor response: Stable disease

Analyses were conducted for the entire cohort (N=12) for secondary objectives.

Total Cohort

Nine of 12 patients had measureable disease post-surgery and were followed with serial MRIs.

Assessment of Tumor Response.

Progression-free Survival

Overall Survival

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy. The unresectable cohort was not able to be opened due to limited product availability.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Resectable Disease

Cohort 1: 0.5x10^8/NSCs/6.25x10^10 vp

Cohort 2: 1.0x10^8 NSCs/1.25x10^10 vp

Cohort 3: 1.5x10^8 NSCs/1.875x10^10 vp

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Virus Diseases

Adenocarcinoma, Clear Cell

Vaccinia

Adenomyoepithelioma

Fallopian Tube Neoplasms

Adenocarcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Epithelial-myoepithelial Carcinoma

Anti-Infective Agents

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Bevacizumab

Carboplatin

Doxorubicin

Liposomal doxorubicin

Cisplatin

Immunomodulating Agents

Taxane

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0

Platinum-doublet \& bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5

Physician's Choice of chemotherapy \& bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).

Olvi-Vec is an engineered oncolytic vaccinia virus

olvimulogene nanivacirepvec

Platinum chemotherapy: carboplatin (preferred) or cisplatin

Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin

Bevacizumab (or biosimilar)

Stefanie White

Jennifer M Scalici, MD

Claudia Al Khairi

Setsuko K. Chambers, MD

Edward Wang, MD, PhD

Alexandrea Cronin

Michael McHale, MD

Ramez Eskander, MD

Esmeralda Martinez

Alberto Mendivil, MD

Krishnansu S. Tewari, MD

Karla Hernandez-Cruz

Robert W Holloway, MD

Monica Rengifo Pardo, MD

Matthew L. Anderson, MD, PhD

Megan Indermaur, MD

Rebekah Little, CRC

Cheri West, RN

Jessica E. Parker, MD

Lyudmila Igorevna Kalnitskaya, MBA, MS

James F Barter, MD

Robert Morris, MD

Linda Odibo

Premal Thaker, MD

Crystal Tindall, BSN, RN

Jessica Black

Dan-Arin Silasi, MD

Peter Lim, MD

Leah Wilson

Erin K Crane, MD

Jackie Ludwig

Peter Rose, MD

Daniel Geyer

Tammy Bonham

Thomas J. Reid, MD

Debra Richardson, MD

Ashma Acharya

Sarah Crafton, MD

Crystal Knox

Whitney S Graybill, MD

Stephen DePasquale, MD

Kim Donelson, LPN CCRP

Jodie Mactagone, CRC

Melanie Bergman, MD

The OnPrime study is a multi-center, randomized open-label phase 3 study evaluating the safety and efficacy of Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab compared to the Active Comparator Arm with Physician's Choice of chemotherapy and bevacizumab in women diagnosed with platinum-resistant/refractory ovarian cancer (includes fallopian tube cancer and primary peritoneal cancer). This Phase III trial builds on the efficacy and safety data reported in the previous Phase II VIRO-15 trial with promising objective response rate and progression-free survival observed in heavily pre-treated patients with platinum-resistant/refractory ovarian cancer. The phase II results also showed that the intra-peritoneal route of delivery was efficient in generating tumor cell killing and immune activation, and led to clinical reversal of platinum-resistance or refractoriness in this difficult-to-treat patient population.

Olvi-Vec (olvimulogene nanivacirepvec, aka GL-ONC1, laboratory name: GLV-1h68) is an oncolytic vaccinia virus-based immunotherapy. This study is to test the hypothesis that the combination of Olvi-Vec followed by further chemotherapy is particularly effective against established tumors by virus-mediated immune activation and re-sensitization of tumor cells to chemotherapy. Participant population includes histologically confirmed non-resectable platinum-resistant/refractory ovarian cancer (PRROC). Determination of progression-free survival, safety and overall survival are key objectives. Participants randomized into the Experimental Arm will receive a single-cycle (2 infusions on two consecutive days) of Olvi-Vec through an intraperitoneal catheter. The catheter is then removed, and patients receive systemically administered platinum-doublet chemotherapy and bevacizumab. The control arm receives the Physician's Choice of chemotherapy and bevacizumab at the same dose and schedule. Biological samples will be obtained from some Experimental Arm participants for virus-shedding testing. Assessment of response to treatment in both arms will be by RECIST 1.1 and iRECIST as assessed by Blinded Independent Central Review. Maintenance/continued treatment with non-platinum chemotherapy and bevacizumab is dependent on a participant being clinically stable until confirmed progressive disease by iRECIST or can no longer tolerate therapy.

Dr. Robert W. Holloway (AdventHealth Cancer Institute, Orlando, FL) will serve as the National Principal Investigator for this Phase 3 study in PRROC.

Randomization (2:1) is either into the Experimental Arm which is Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or into the Active Comparator Arm which is Physician's Choice of chemotherapy and bevacizumab.

Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)

A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Physician's Choice of Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)

To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.

Determine safety and tolerability of administering multiple doses of Olvi-Vec via intraperitoneal catheter in combination with platinum-doublet and bevacizumab (or biosimilar) as assessed by CTCAE v. 5.0 following initiation of study treatment until end of study participation.

Time from date of first response until the first date of progressive disease based on radiological assessment.

Time from randomization to first documented disease progression based on radiological assessment or death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma	NCT03072134	Glioma Anaplastic Astr... Anaplastic Olig... Anaplastic Olig... Glioblastoma Mu... Astrocytoma, Gr... Astrocytoma, Gr... Brain Cancer	Neural stem cel...	18 Years -	Northwestern University
Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)	NCT05281471	Platinum-resist... Platinum-refrac... Fallopian Tube ... Primary Periton... High-grade Sero... Endometrioid Ov... Ovarian Clear C...	olvimulogene na... Platinum chemot... Non-platinum ch... Bevacizumab (or...	18 Years -	Genelux Corporation
TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 Monotherapy	NCT04695327	Solid Tumor	TILT-123	18 Years -	TILT Biotherapeutics Ltd.
Phase I Endovenous Administration of Oncolytic Adenovirus ICOVIR-5 in Patients With Advanced or Metastatic Melanoma	NCT01864759	Locally Advance...	ICOVIR-5	18 Years -	Institut Català d'Oncologia
A Study of OBP-301 With Radiation Therapy in Patients With Esophageal Cancer	NCT03213054	Esophageal Canc...	OBP-301 Radiation	20 Years - 89 Years	Oncolys BioPharma Inc
A Study of OBP-301 With Radiation Therapy in Patients With Esophageal Cancer	NCT03213054	Esophageal Canc...	OBP-301 Radiation	20 Years - 89 Years	Oncolys BioPharma Inc
Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma	NCT06169280	Glioma, Maligna... New Diagnosis T...	NSC-CRAd-S-pk7 N-acetylcystein...	18 Years -	Northwestern University
GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer	NCT02759588	Ovarian Cancer Peritoneal Carc... Fallopian Tube ...	GL-ONC1 alone, ...	21 Years -	Genelux Corporation
Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma	NCT06169280	Glioma, Maligna... New Diagnosis T...	NSC-CRAd-S-pk7 N-acetylcystein...	18 Years -	Northwestern University

Spots Global Cancer Trial Database for virotherapy

Every month we try and update this database with for virotherapy 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 virotherapy

Every month we try and update this database with for virotherapy 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 virotherapy 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.