Phase I/II Study of AloCelyvir in Patients With Metastatic Uveal Melanoma

NCT05047276 | Unknown Phase 1

• 1 other identifier: PULSE-UM
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, single arm, single center, phase I/II study of AloCelyvir in subjects with mUM to the liver, the main site for M1 in this disease. This study is divided into 3 phases: Screening, Treatment, and Follow-up. After informed consent is obtained, subjects will enter in the Screening phase to assess eligibility criteria and perform a mandatory tumor biopsy. Upon meeting criteria, eligible subjects will be entered into the Treatment phase. Patients will receive AloCelyvir in weekly intravenous infusions at doses of 0.5x106 cells/kg for 8 weeks. After 4 first treatment doses a new tumor biopsy will be mandatory. Treatment will be maintained for 2 months (8 weeks) but can be stopped earlier if disease progression, unacceptable toxicity, or patient withdrawal. Subjects that are no longer receiving AloCelyvir will enter the Follow-up phase. Subjects that are no longer receiving AloCelyvir because of unacceptable toxicity or due to investigator judgment will undergo radiological evaluations of the tumor every 8 weeks during the first 12 months (48 weeks), and then every 12 weeks until the progression of disease (progression follow-up). Subjects that are no longer receiving Alocelyvir because of progression will enter the long term OS follow-up until their death or until the end of the study, whatever happens before. Subjects who have switched to an alternative treatment without disease progression will receive a formal follow-up with images tests until progression, and after progression long term follow up to record the date of death.

Conditions

Uveal Melanoma, Metastatic

Keywords

Uveal Melanoma, Advanced therapy, AloCelyvir, Icovir-5, Mesenchymal Stem Cells, Oncolytic virus

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Objective Response Rate (ORR) is defined as the proportion of patients with at least one visit response of CR or PR that is confirmed at least 4 weeks later. Where PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters as long as criteria for PD are not met and CR is disappearance of all target lesions. Any pathological lymph nodes selected as target lesions must have a reduction in short axis to \<10mm. Following RECIST 1.1 criteria, for non-randomised trials where response is the primary endpoint, confirmation of PR and CR is required to ensure responses identified are not the result of measurement error. ORR defined in this manner is a direct measure of drug antitumor activity, which can be evaluated in a single-arm study, providing an accurate assessment of a subrogate efficacy endpoint.

  6 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  3 months / 6 months

• Overall Survival (OS)

  1 year / 2 years

• Evaluate Safety

  2 years

Study Arms (1)

AloCelyvir

EXPERIMENTAL

Delivery of Icovir-5 by mesenchymal carrier cells in uveal melanoma patients with hepatic metastases.

Biological: AloCelyvir

Interventions

AloCelyvir BIOLOGICAL

Delivery of Icovir-5 by mesenchymal carrier cells in uveal melanoma patients with hepatic metastases.

AloCelyvir

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed metastatic uveal melanoma with measurable disease not eligible for curative therapy.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, PET/CT, MRI, or calipers by clinical exam. Patients must have at least 1 biopsiable liver metastasis.

You may not qualify if:

• Patients must be 18 years of age or older at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations not performed according to normal practice. Patient must consent for liver metastasis biopsies donation at day 0 and day +28 since treatment initiation.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) \> 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with Coordinating Investigator.
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3 x ULN.
• Creatinine clearance ≤1.5 x ULN or a calculated by Cockcroft-Gault \>60 ml/min/1,73.
• Female participant has a negative serum pregnancy test prior to revieving study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 150 days after the last dose of study treatment, or is of non-childbearing potential.
• Amenorrheic for ≥1 year in the absence of chemotherapy and/or hormonal treatments,
• Luteinizing hormone (LH) and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range,
• Radiation induced oophorectomy with last menses \>1 year ago,
• Chemotherapy induced menopause with \>1 year interval since last menses,

Sponsors & Collaborators

• José María Piulats Rodríguez: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

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MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Josep M Piulats, MD, Phd

  ICO, IDIBELL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Josep M Piulats, MD, Phd

CONTACT

+34 93 2607744; jmpiulats@iconcologia.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor's representative

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 17, 2021
• Study Start: October 1, 2021
• Primary Completion: June 30, 2023
• Study Completion: December 31, 2024
• Last Updated: September 17, 2021

Record last verified: 2021-09

Locations

ES (1)