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Uveal MelanomaPhase 1CLEVERNCT03408587

CAVATAK® and Ipilimumab in Uveal Melanoma Metastatic to the Liver (VLA-024 CLEVER)

A Phase 1 study testing CVA21 and Ipilimumab in people with Uveal Melanoma and Liver Metastases, run by Viralytics at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label Phase 1b clinical study of ipilimumab in combination with intravenous CVA21 in subjects who have uveal melanoma metastatic to liver. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveal Melanoma, Liver Metastases
What is being tested?
CVA21 and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
3 sitesUnited States
Study dates
29 Jan 2018to 22 May 2019
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologic or cytologically confirmed diagnosis of uveal melanoma with measurable disease (based on RECIST 1.1 criteria) in the liver (by CT, PET/CT or MRI) at the time of screening.
  • Patients that have had prior treatment must show disease progression during or following the last treatment according to RECIST 1.1 criteria.
  • Men and women ≥ 18 years of age.
  • The subject has a life expectancy of greater than 12 weeks.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Adequate organ function as defined by and obtained within 28 days of starting treatment:
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  • Absolute neutrophil count ≥ 1,500 /mcl
  • WBC ≥ 3.0 x 10e9/L
  • Platelets ≥ 100,000 /mcl
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 x ULN
  • Albumin > 3 g/dL
  • Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin > 1.5 x ULN
  • AST and ALT ≤ 5 x ULN
  • INR or PT ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT are within therapeutic range of intended use of anticoagulants.
  • aPTT ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT are within therapeutic range of intended use of anticoagulants.
  • Prior therapy with an immune checkpoint inhibitor therapy is allowable. A 6-week washout period will be required for those with prior PD-1 or PD-L1 treatment.
  • Female subjects of child-bearing potential must have a negative urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female and Male subjects of childbearing potential must be willing to use an adequate method of contraception, starting with the first dose of study drug through 4 weeks after the last dose of study drug. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • The subject is capable of understanding and complying with protocol requirements.
  • The subject or the subject's legally acceptable representative provides written, informed consent prior to the initiation of any study procedures.

Who cannot join

  • The subject is a candidate for surgery or loco-regional treatment with curative intent.
  • Subjects with active (i.e. symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, the subject is off corticosteroids for at least 2 weeks and the subject is neurologically stable.
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include cutaneous squamous cell or basal cell carcinoma that has undergone potentially curative therapy or in-situ cervical cancer.
  • Known history of Human Immunodeficiency Virus (HIV, HIV 1/2 antibodies), known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA [qualitative] is detected).
  • Current systemic steroid therapy other than physiologic replacement (i.e. prednisone ≤ 10 mg or equivalent). Inhaled or topical steroid use is allowed.
  • Active auto-immune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
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  • Active colitis or previous immune-mediated colitis that has not resolved to grade 1 or less.
  • Chemotherapy, targeted small molecule therapy, radiation therapy, hormonal treatment or immunotherapy within 21 days prior to initiation of treatment. A 6-week washout period will be required for those with prior PD-1 or PD-L1 treatment. Subjects must have resolution of toxic effect(s) of the most recent therapy to Grade 1 or less. Exceptions are subjects with ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy who are permitted in the study. If the subject received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or any complications from the intervention.
  • Pregnancy, breastfeeding, or expectation to conceive or father children within the projected duration of the trial, starting with the screening visit through 4 weeks after the last dose of study treatment.
  • Known sensitivity to any of the products or components to be administered during dosing.
  • Participation in a study of an investigational agent or device within 4 weeks of Day 1.
  • Subjects with any other concurrent, uncontrolled illness, including known psychiatric or substance abuse disorders which may interfere with the ability of the subject to cooperate and participate in the trial. Other examples of such conditions would include unstable angina, myocardial infarction (MI) or cerebrovascular accident (CVA) within 6 months of study entry.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Patients with tumors lying close to an airway, major blood vessel or spinal cord that, in the opinion of the investigator, could cause occlusion or compression in the case of swelling, or erosion into a major vessel in the case of necrosis.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

Other trials in United States

About this study

Official title: An Open-Label Phase 1b Clinical Study of Intravenous CAVATAK® (Coxsackievirus A21, CVA21), in Combination With Ipilimumab in Subjects With Uveal Melanoma Metastatic to Liver (VLA-024 CLEVER)

This is an open-label Phase 1b clinical study of ipilimumab in combination with intravenous CVA21 in subjects who have uveal melanoma metastatic to liver.

Read the detailed description

This is an open-label Phase 1b clinical study of ipilimumab in combination with intravenous CVA21 in subjects who have uveal melanoma metastatic to liver. Subjects will receive up to 8 cycles of CVA21 at a planned dose of 1 x 10e9 TCID50 per infusion, with the first cycle being a 28-day cycle consisting of an intravenous infusion on Days 1, 3, 5 and 8 and subsequent cycles every 21 days from Day 8.

Ipilimumab will be given by intravenous administration at a dose of 3mg/kg, for a maximum of 4 doses, given on Days 8, 29, 50 and 71. On days when both CVA21 and ipilimumab are given, CVA21 will be given first.

Subjects will be monitored for treatment toxicity using the current version of CTCAE.

Being tested
CVA21, Ipilimumab
Keywords
CVA21, CAVATAK, Coxsackievirus, ocular, eye, ipilimumab, yervoy, oncolytic, virus, checkpoint, CTLA-4
Medical subject headings
Uveal Melanoma, Coxsackievirus Infections, Virus Diseases, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CVA21Biological

    Also called CAVATAK, Coxsackievirus A21

    Oncolytic virus

  • IpilimumabBiological

    Also called Yervoy

    Fully human IgG1 monoclonal antibody that binds to the CTLA-4 receptor expressed on activated T cells.

Study groups in NCT03408587
Study groupRoleWhat they receive
CVA21 / IpilimumabExperimentalSubjects will receive up to 8 cycles (Day 155) of intravenous CVA21 and 4 doses of ipilimumab (Days 8, 29, 50 and 71).
Receives: Biological: CVA21; Biological: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of treatment-related adverse events as assessed using the current NCI-CTCAE.

    Treatment-emergent adverse events (TEAEs) are defined as AEs that start on or after the first day of study treatment and within 30 days of the last administration of study treatment. The incidence of TEAEs will be summarized based on the number and percentage of subjects who experience events classified by MedDRA system organ class and preferred term.

    Measured: 30 days from the last administration of study treatment

Secondary outcomes (1)

  1. Overall Response Rate

    Objective responses will be assessed according to immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jan 2018
  2. Study start29 Jan 2018
  3. Primary completion22 May 2019
  4. Study completion22 May 2019

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03408587
Sponsor's protocol ID
V937-010
Other IDs
VLA-024
Acronym
CLEVER
Status last verified
May 2023
First submitted
10 Jan 2018
Last updated
6 May 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lutzky J, Sullivan RJ, Cohen JV, Ren Y, Li A, Haq R. Phase 1b study of intravenous coxsackievirus A21 (V937) and ipilimumab for patients with metastatic uveal melanoma. J Cancer Res Clin Oncol. 2023 Aug;149(9):6059-6066. doi: 10.1007/s00432-022-04510-3. Epub 2023 Jan 18.

    PubMed 36651961

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CVA21 and Ipilimumab in people with Uveal Melanoma and Liver Metastases, run by Viralytics at 3 sites 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 21 inclusion and 14 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: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of treatment-related adverse events as assessed using the current NCI-CTCAE. (time frame: 30 days from the last administration of study treatment). 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 NCT03408587, which also lists 1 linked publication.

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 6 May 2023.

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