A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (CALM)
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|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|
- 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.
- 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.
|Study Start Date:||October 2011|
|Study Completion Date:||April 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Intratumoral injection
Each patient will receive 4 separate Coxsackievirus A21 (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) until confirmed disease progression or development of excessive toxicity. Subjects with stable disease or better at Day 127 were eligible to receive up 9 more sets of CVA21 administrations under an extension protocol (VLA-008).
Biological: Coxsackievirus A21 (CVA21)
CVA21 is a live oncolytic virus preparation derived from the non-genetically altered prototype Kuykendall strain of Coxsackievirus A21.
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 trial for a further 6 weeks, when his/her disease status will be confirmed prior to the scheduled treatment. If disease progression is confirmed, the patient will cease treatment but will remain on the study and be observed for efficacy and safety until initiation of treatment with non-CVA21 anticancer therapies. However, survival will be followed until death. If stable disease or better (CR or PR) is observed at this time, the patient will continue treatment as per the protocol. Complete and partial responses will be confirmed at the next contrast-enhanced CT or MRI scan analysis.
Patients who have evidence of biologic activity, i.e., tumor inflammatory reaction and/or stable disease or better, at 18 weeks (Day 127) are eligible to participate in the extension trial in which they will continue to receive IT injections of CVA21 every 3 weeks up to a total of 1 year of therapy from the first injection.
Throughout the trial, immunological responses to the tumor and CVA21 will be monitored.
After the full CVA21 injection schedule has been completed, patients will be followed at 12-weekly intervals beginning on Day 169 for a total of 12 months according to the schedule for safety assessment and indefinitely for survival. Patients with progressive disease (but without rapid clinical deterioration) at 6 months (Day 169) will have a further tumor assessment 6 weeks later for confirmation or continuation of observation for duration of disease control and all subjects will be followed for survival. Patients who are withdrawn from treatment with CVA21 during the treatment phase must also be followed up every 6 weeks for 12 weeks for safety and for survival.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01227551
|United States, California|
|Moores UCSD Cancer Center|
|La Jolla, California, United States, 92093|
|St Mary's Medical Center|
|San Francisco, California, United States, 94117|
|United States, Florida|
|Mount Sinai Medical Center|
|Miami Beach, Florida, United States, 33140|
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|Oncology Specialists, SC|
|Niles, Illinois, United States, 60714|
|United States, Indiana|
|Investigative Clinical Research of Indiana|
|Indianapolis, Indiana, United States, 46260|
|United States, New Jersey|
|Atlantic Melanoma Center|
|Morristown, New Jersey, United States, 07962|
|United States, Oregon|
|Providence Cancer Center|
|Portland, Oregon, United States, 97213|
|United States, Texas|
|Mary Crowley Cancer Research Centers|
|Dallas, Texas, United States, 75201|
|United States, Utah|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Robert Andtbacka, MD||Associate Professor|