MelanomaPhase 1NCT03712358
PVSRIPO for Patients With Unresectable Melanoma
A Phase 1 study testing PVSRIPO in people with Melanoma, run by Istari Oncology, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- PVSRIPO
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Nov 2018to 23 Mar 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Undergone prior vaccination against PV and received a boost immunization with trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to administration of PVSRIPO (within 6 months of PVSRIPO retreatment).
- Note: Patients who are unsure of their prior vaccination status/who have not been vaccinated must provide proof of vaccination and/or evidence of anti-PV immunity prior to enrollment, as applicable.
- 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, recurrent, melanoma, stage IIIB, IIIC, 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 positron emission tomography (PET) scan, and MRI of the brain within 4 weeks prior to administration of study drug).
- Patients with BRAF mutations, must have failed at least 2 lines of therapy, specifically one BRAF targeted therapy and at least one anti-PD-1 based therapy. For BRAF wild type, patients must have failed at least one anti-PD-1 based therapy.
- Patient must be ≥ 18 years of age.
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- Patient must have an Eastern Cooperative Oncology Group (ECOG) / Zubrod status of 0-1.
- Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the immune-related response criteria (irRC).
- 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 (Cohorts 0 and possibly 1). For cohorts where 2 or 3 injections are planned (Cohorts 1 and 2), the patient must have at least 2 injectable melanoma lesions (when 2 doses are planned) or ≥3 injectable melanoma lesions when at least 3 doses are planned in different lesions (Cohorts 2 through 4).
- Note: PVSRIPO retreatment requires ≥2 lesions amenable to injection.
- At least one measurable lesion that will not be injected.
- 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
- White blood count (WBC) of > 2000 m3
- Absolute neutrophil count (ANC) > 1,000/mm3
- Platelet count > 75,000/mm3
- Total bilirubin < 2.0 x ULN
- Alanine aminotransferse (ALT) and aspartate aminotransferance (AST) < 2.5 x the ULN
Who cannot join
- Females who are pregnant or breast-feeding.
- Adults of reproductive potential not employing an effective method of birth control.
- Patients with severe, active co-morbidity, defined as follows:
- Patients with an active infection requiring treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C).
- 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 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 (HgbA1c>7).
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- Patients with albumin allergy.
- Autoimmune disease: History of or current active autoimmune diseases, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome)]. Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.
- Known immunosuppressive disease, human immunodeficiency virus (HIV) infection, or chronic Hepatitis B or C.
- Patients with a previous history of neurological complications due to PV 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. Toxicities must have resolved to CTCAE grade 1 or less with the following exceptions (alopecia, fatigue, vitiligo).
- Patients with undetectable anti-tetanus toxoid IgG.
- Patients with known history of agammaglobulinemia.
- Patients on greater than 10 mg per day of prednisone within the 2 weeks prior to admission for PVSRIPO injection.
- 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.
- Clinically active cerebral or bone metastases.
- Greater than 3 visceral metastases (this does not include nodal metastases associated with visceral organs).
- Prior allogeneic stem cell transplantation.
- Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating immune related adverse events (irAE), adrenal insufficiencies, or if administered at doses of prednisone 10 mg daily or equivalent.
- Active clinically serious infection > CTCAE Grade 2.
- Antineoplastic therapy, radiotherapy, or any other investigational drug within 15 days prior to first study drug administration.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase I Trial of PVSRIPO for Patients With Unresectable Melanoma
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.
Read the detailed description
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 dose-limiting toxicities (DLT) 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.
- Conditions
- Melanoma
- Being tested
- PVSRIPO
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PVSRIPOBiological
Intralesional injection of PVSRIPO.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 0 (PVSRIPO) | Experimental | A single dose of PVSRIPO into a single lesion. Receives: Biological: PVSRIPO |
| Cohort 1 (PVSRIPO) | Experimental | A single dose of PVSRIPO into 2 different lesions, 21 days apart, when applicable per dose escalation guidelines. Receives: Biological: PVSRIPO |
| Cohort 2 (PVSRIPO) | Experimental | A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines. Receives: Biological: PVSRIPO |
| Cohort 3 (PVSRIPO) | Experimental | A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines. Receives: Biological: PVSRIPO |
| Cohort 4 (PVSRIPO) | Experimental | 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. Receives: Biological: PVSRIPO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients With Dose Limiting Toxicity by Cohort
To characterize the safety and tolerability of PVSRIPO in American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC, or IV melanoma.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start26 Nov 2018
- Primary completion23 Mar 2021
- Study completion23 Mar 2021
Why it stopped: Study closed to enrollment due to business decision prior to enrolling Cohort 4
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istari Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Duke University, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Lisa Franklin, Study director, Istari Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03712358
- Sponsor's protocol ID
- Pro00090774
- Other IDs
- K08CA237726
- Status last verified
- Apr 2024
- First submitted
- 5 Oct 2018
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Brown MC, Beasley GM, McKay ZP, Yang Y, Desjardins A, Randazzo DM, Landi D, Ashley DM, Bigner DD, Nair SK, Gromeier M. Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils. J Immunother Cancer. 2023 Apr;11(4):e006463. doi: 10.1136/jitc-2022-006463.
PubMed 37072349Beasley GM, Brown MC, Farrow NE, Landa K, Al-Rohil RN, Selim MA, Therien AD, Jung SH, Gao J, Boczkowski D, Holl EK, Salama AKS, Bigner DD, Gromeier M, Nair SK. Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma. J Immunother Cancer. 2022 Sep;10(9):e005052. doi: 10.1136/jitc-2022-005052.
PubMed 36175036Beasley GM, Nair SK, Farrow NE, Landa K, Selim MA, Wiggs CA, Jung SH, Bigner DD, True Kelly A, Gromeier M, Salama AK. Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma. J Immunother Cancer. 2021 Apr;9(4):e002203. doi: 10.1136/jitc-2020-002203.
PubMed 33875611
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of PVSRIPO for Patients With Unresectable Melanoma
- ClinicalTrials.gov ID
- NCT03712358
- Acronym / sponsor ID
- Pro00090774
- Conditions
- Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study closed to enrollment due to business decision prior to enrolling Cohort 4
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Istari Oncology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Duke University, National Cancer Institute (NCI)
- Study start
- 26 Nov 2018 (actual)
- Primary completion
- 23 Mar 2021 (actual)
- Study completion
- 23 Mar 2021 (actual)
- First posted
- 19 Oct 2018 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 dose-limiting toxicities (DLT) 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 0 (PVSRIPO) | Experimental | Biological: PVSRIPOA single dose of PVSRIPO into a single lesion. |
| Cohort 1 (PVSRIPO) | Experimental | Biological: PVSRIPOA single dose of PVSRIPO into 2 different lesions, 21 days apart, when applicable per dose escalation guidelines. |
| Cohort 2 (PVSRIPO) | Experimental | Biological: PVSRIPOA single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines. |
| Cohort 3 (PVSRIPO) | Experimental | Biological: PVSRIPOA single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines. |
| Cohort 4 (PVSRIPO) | Experimental | Biological: PVSRIPOA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Undergone prior vaccination against PV and received a boost immunization with trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to administration of PVSRIPO (within 6 months of PVSRIPO retreatment).
- 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, recurrent, melanoma, stage IIIB, IIIC, 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 positron emission tomography (PET) scan, and MRI of the brain within 4 weeks prior to administration of study drug).
- Patients with BRAF mutations, must have failed at least 2 lines of therapy, specifically one BRAF targeted therapy and at least one anti-PD-1 based therapy. For BRAF wild type, patients must have failed at least one anti-PD-1 based therapy.
- Patient must be ≥ 18 years of age.
Key exclusion criteria (22 listed)
- Females who are pregnant or breast-feeding.
- Adults of reproductive potential not employing an effective method of birth control.
- Patients with severe, active co-morbidity, defined as follows:
- Patients with a previous history of neurological complications due to PV 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. Toxicities must have resolved to CTCAE grade 1 or less with the following exceptions (alopecia, fatigue, vitiligo).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PVSRIPOIntralesional injection of PVSRIPO. | Biological | Cohort 0 (PVSRIPO), Cohort 1 (PVSRIPO), Cohort 2 (PVSRIPO), Cohort 3 (PVSRIPO), Cohort 4 (PVSRIPO) |
Primary outcome
Proportion of Patients With Dose Limiting Toxicity by Cohort
Time frame: 24 months
To characterize the safety and tolerability of PVSRIPO in American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC, or IV melanoma.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37072349Brown MC, Beasley GM, McKay ZP, Yang Y, Desjardins A, Randazzo DM, Landi D, Ashley DM, Bigner DD, Nair SK, Gromeier M. Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils. J Immunother Cancer. 2023 Apr;11(4):e006463. doi: 10.1136/jitc-2022-006463.
- Derived from this study: PubMed 36175036Beasley GM, Brown MC, Farrow NE, Landa K, Al-Rohil RN, Selim MA, Therien AD, Jung SH, Gao J, Boczkowski D, Holl EK, Salama AKS, Bigner DD, Gromeier M, Nair SK. Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma. J Immunother Cancer. 2022 Sep;10(9):e005052. doi: 10.1136/jitc-2022-005052.
- Derived from this study: PubMed 33875611Beasley GM, Nair SK, Farrow NE, Landa K, Selim MA, Wiggs CA, Jung SH, Bigner DD, True Kelly A, Gromeier M, Salama AK. Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma. J Immunother Cancer. 2021 Apr;9(4):e002203. doi: 10.1136/jitc-2020-002203.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Franklin study director
Istari Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PVSRIPO in people with Melanoma, run by Istari Oncology, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients With Dose Limiting Toxicity by Cohort (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03712358, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.