PVSRIPO in Combination With Nivolumab in Melanoma

NCT04125719 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pro00101803
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Assess the percent of adverse events related to the combination of PVSRIPO + nivolumab in the treatment of patients with recurrent melanoma.

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

  36 months

Study Arms (2)

Primay PD-1 resistance

EXPERIMENTAL

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

Biological: PVSRIPO; Drug: Nivolumab

Secondary PD-1 resistance

EXPERIMENTAL

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

Biological: PVSRIPO; Drug: Nivolumab

Interventions

PVSRIPO BIOLOGICAL

Intralesional injection of PVSRIPO

Primay PD-1 resistance; Secondary PD-1 resistance

Nivolumab DRUG

Nivolumab infusion

Also known as: Opdivo

Primay PD-1 resistance; Secondary PD-1 resistance

Eligibility Criteria

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

You may qualify if:

• Positive serum anti-poliovirus antibody 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.
• Patient must have histologically proven unresectable melanoma, stage IIIB, IIIC, IIID, or stage IV (AJCC version 8 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 progressed following ≥1 line of one prior systemic therapy, including immune checkpoint inhibitor (eg, anti- PD-1, ipilimumab, or anti PD-1 plus ipilimumab); and if BRAF V600 mutation-positive, after a BRAF inhibitor or BRAF inhibitor in combination with MEK inhibitor. Patients last dose of systemic therapy must have been within 9 months prior to signing consent for this study. Patients treated in the adjuvant setting and develop recurrence are also allowed.
• 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.
• Patient must be ≥18 years of age.
• Patient must have an ECOG/Zubrod status of 0-1.
• Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the iRECIST criteria. The sum of target lesion diameters should be at least 10 mm.
• At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion ≥ 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of ≥ 10 mm.
• Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN).
• Patient must have adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin ≥ 9.0 g/dl, patients may be transfused to meet this criteria
• Lymphocyte count ≥ 0.5 x 109/L (500 µL)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500 µL)
• Platelet count ≥ 100 x 109/L (100,000 µL) without transfusion

You may not qualify if:

• Symptomatic, untreated, or actively progressing CNS metastases. Patients with a history of treated CNS lesions are eligible, provided that all of the following criteria are met:
• The patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
• Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
• History of leptomeningeal disease.
• Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry.
• Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• a. Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN).
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

Sponsors & Collaborators

• Darell Bigner: lead
• Duke University: collaborator
• Istari Oncology, Inc.: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Georgia Beasley

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Edwin L. Jones, Jr. and Lucille Finch Jones Cancer Research Professor

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 14, 2019
• Study Start: June 1, 2020
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: February 11, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)