Clinical Trial: A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2 Study of the Efficacy and Safety of Intratumoral CAVATAK™ (Coxsackievirus A21, CVA21) in Patients With Stage IIIc and Stage IV Malignant Melanoma

Brief Summary: The purpose of this study is to assess the clinical efficacy of Intratumoral (IT) CVA21 in terms of immune-related Progression-Free Survival (irPFS) at 6 months as monitored via immune-related Response Criteria [irRECIST 1.1] (revised Response Evaluation Criteria In Solid Tumors [RECIST] 1.1).

Detailed Summary:

This is a multicenter, open-label, 2-stage, single-arm efficacy and safety study. Approximately 63 patients with histologically proven stage IIIc or stage IV melanoma who fail to qualify for curative surgery and who bear one or more tumors that are accessible for direct injections and at least one measurable lesion by RECIST 1.1 criteria will be considered.

Prospective patients will attend the study center for initial screening within 28 days prior to treatment with CVA21. They will have the nature of the study and its procedures and risks fully explained. All patients must provide a written informed consent to participate in the study.

The dose of CVA21 for this study is 3 x 108 TCID50 (about 4.5 x 106 TCID50/kg for a 70-kg patient) by IT administration. Each patient will receive 4 separate CVA21 administrations in the first 8 days on trial (Days 1, 3, 5 and 8), followed by a fifth dose 2 weeks later (Day 22) and further administrations at 3 weekly intervals (Days 43, 64, 85, 106 and 127, up to a maximum of 10 sets of injections) or until confirmed disease progression or development of excessive toxicity.

Disease status will be assessed by contrast-enhanced computerized tomography (CT) or magnetic resonance imaging (MRI) scan and/or direct caliper measurement (and ultrasound assistance, if necessary) and categorized by immune-related RECIST 1.1 criteria prior to commencing treatment (baseline) and at Days 43, 85, 127 and 169 and 12-weekly intervals thereafter until disease progression. At 2 years, intervals can increase to 6 months.

At 12 weeks post-commencement of treatment (Day 85), if a patient's disease status is classed as progressive disease (but without rapid clinical deterioration) the patient may remain on the tria
Sponsor: Viralytics

Current Primary Outcome: Percentage of Participants With Immune-related Progression-Free Survival (irPFS) at 6 Months [ Time Frame: 6 months ]

To assess the clinical efficacy of Intratumoral (IT) CVA21 in terms of immune-related Progression-Free Survival (irPFS) at 6 months.


Original Primary Outcome: Immune-related Disease Control Rate (irDCR) at 6 months [ Time Frame: 6 months ]

The clinical efficacy of intratumoral (IT) CVA21 is assesed in terms of Disease Control Rate (i.e., Complete Response [irCR] + Partial Response [irPR] + Stable Disease [irSD]) as monitored via immune-related Response Criteria [irRC] (immune-related RECIST 1.1) at 6 months, i.e., immune-related Disease Control Rate (irDCR) at 6 months


Current Secondary Outcome: Durable Response Rate [ Time Frame: 6 months or more ]

Per Immune-Related Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI or calipers: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Durable Response Rate (DRR) = CR + PR.


Original Secondary Outcome:

  • Durable Response Rate at 6 months [ Time Frame: 6 months ]
    The clinical efficacy of IT CVA21 is assessed in terms of Durable Response Rate (DRR) at 6 months
  • 6 month Progression-Free Survival, 1 year Survival, Overall Survival [ Time Frame: 6 months and 1 year ]
    The clinical efficacy if IT CAVATAK is assessed in terms of Progression-Free Survival at 6 months, 1 - year survival and Overall Survival (OS)
  • Safety of IT CAVATAK administration [ Time Frame: 1 year ]
    The safety of IT CAVATAK administration is assessed in terms of adverse events, viral biodistribution and serum antibody responses to CVA21
  • Quality of Life [ Time Frame: 1 year ]
    The impact of IT CAVATAK administration on Quality of Life is assessed using the FACT-BRM Questionaire.


Information By: Viralytics

Dates:
Date Received: October 20, 2010
Date Started: October 2011
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017