PVSRIPO in Combination With Nivolumab in Melanoma

Withdrawn before enrolling · Phase 1

Conditions studied: Melanoma

In brief

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.

Key facts

Study ID

NCT04125719

Run by

Darell Bigner

People needed

0

Starts

2020-06-01

Expected to finish

2024-10-01

Last updated by the study team

2020-02-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions:
• i. Patients with documented liver metastases: AST and ALT ≤ 5 x ULN ii. Patients with documented liver or bone metastases: ALP ≤ 5 x ULN f. Serum bilirubin ≤ 1.5 x ULN with the following exception: i. Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN g. Serum creatinine ≤ 1.5 x ULN h. Serum albumin ≥ 25 g/L (2.5 g/dL) i. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
• Patients must have a life expectancy of > 6 months.
• Patient must provide a signed and dated written informed consent prior to registration and any study-related procedures.
• Ability to read and understand English and the ability to complete paper and electronic survey assessments.
• Ability to comply with the study protocol, in the investigator's judgement.
• For women of childbearing potential:
• Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of study treatment. Note: A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
• i. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

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:
• i. Rash must cover < 10% of body surface area ii. Disease is well-controlled at baseline and requires only low-potency topical corticosteroids iii. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• History of a Positive HIV test
• Known active hepatitis B virus (HBV) infection (chronic or acute).
• a. Patients who have had a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test are eligible for the study.
• Known active hepatitis C virus (HCV) infection.
• a. If potential subjects have a history of a positive HCV antibody test, but negative HCV RNA test, subject may be eligible for the study
• Active tuberculosis
• Significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.

Where it is running

• Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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