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

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Brief Title

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

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)

Brief 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.
    

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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Overall Response Rate

Condition

Uveal Melanoma

Intervention

CVA21

Study Arms / Comparison Groups

 CVA21 / Ipilimumab
Description:  Subjects will receive up to 8 cycles (Day 155) of intravenous CVA21 and 4 doses of ipilimumab (Days 8, 29, 50 and 71).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

11

Start Date

January 29, 2018

Completion Date

May 22, 2019

Primary Completion Date

May 22, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Patients that have had prior treatment must show disease progression during or
             following the last treatment according to RECIST 1.1 criteria.

          3. Men and women ≥ 18 years of age.

          4. The subject has a life expectancy of greater than 12 weeks.

          5. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of
             0-1.

          6. Adequate organ function as defined by and obtained within 28 days of starting
             treatment:

               -  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.

          7. 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.

          8. 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.

          9. 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.

         10. The subject is capable of understanding and complying with protocol requirements.

         11. The subject or the subject's legally acceptable representative provides written,
             informed consent prior to the initiation of any study procedures.

        Exclusion Criteria:

          1. The subject is a candidate for surgery or loco-regional treatment with curative
             intent.

          2. 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.

          3. 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.

          4. 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).

          5. Current systemic steroid therapy other than physiologic replacement (i.e. prednisone ≤
             10 mg or equivalent). Inhaled or topical steroid use is allowed.

          6. 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.

          7. Active colitis or previous immune-mediated colitis that has not resolved to grade 1 or
             less.

          8. 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.

          9. 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.

         10. Known sensitivity to any of the products or components to be administered during
             dosing.

         11. Participation in a study of an investigational agent or device within 4 weeks of Day
             1.

         12. 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.

         13. 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.

         14. 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jose Lutzky, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03408587

Organization ID

V937-010

Secondary IDs

VLA-024

Responsible Party

Sponsor

Study Sponsor

Viralytics


Study Sponsor

Jose Lutzky, MD, Principal Investigator, Icahn School of Medicine at Mount Sinai


Verification Date

June 2019