A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )

NCT01227551 | Completed Phase 2 Results DMC

• 2 other identifiers: V937-006VLA-007
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 10

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).

Conditions

Malignant Melanoma

Keywords

Melanoma; CALM

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Immune-related Progression-Free Survival (irPFS) at 6 Months

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

  6 months

Secondary Outcomes (1)

• Durable Response Rate

  6 months or more

Study Arms (1)

Intratumoral injection

EXPERIMENTAL

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)

Interventions

Coxsackievirus A21 (CVA21) BIOLOGICAL

CVA21 is a live oncolytic virus preparation derived from the non-genetically altered prototype Kuykendall strain of Coxsackievirus A21.

Intratumoral injection

Eligibility Criteria

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

You may qualify if:

• Patient with histologically proven stage IIIc or stage IV melanoma who fails to qualify for curative surgery and who bears one or more tumors that are accessible for direct injection
• Patient must have had no more than one previous systemic regimen for management of melanoma; however, adjuvant chemotherapy administered 6 months or longer before entering the trial does not count as a line of treatment
• Absence of circulating serum neutralizing antibodies to CVA21 (titer \< 1:16)
• At least one tumor 0.5 to 10 cm in the longest diameter must be suitable for injection and at least one tumor must be equal to or greater than 1 cm and qualified to be a target lesion for RECIST 1.1 criteria
• Patient must have adequate hematologic, hepatic and renal function, defined as:
• Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L
• Bilirubin \< 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) \< 2.5 x ULN
• Serum creatinine \< 1.5 x ULN; if \> 1.5 x ULN, it must be confirmed that creatinine clearance \> 30 mL/minute
• Serum lactate dehydrogenase (LDH) levels \< or = 1.5 x ULN
• Male or female age 18 years or older
• Performance status (Eastern Cooperative Oncology Group \[ECOG\]) 0 or 1
• Estimated life expectancy of more than 6 months
• Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy
• Patient is able and willing to provide written informed consent to participate in the study
• Fertile males and females must agree to the use of an adequate form of contraception, e.g., condoms for males. A negative pregnancy test is required in female patients of childbearing potential.

You may not qualify if:

• Mucosal or ocular primary tumors
• Bone metastases
• Greater than 3 visceral metastases
• Any visceral metastases \> 10 cm
• Serum anti-CVA21 neutralizing titer of \> 1:16 at baseline
• Presence of any central nervous system (CNS) tumor that has not been stable for at least 3 months off corticosteroids and confirmed by imaging
• Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion into a major vessel in the case of necrosis
• Only measurable tumor had prior local radiotherapy without subsequent nodule progression
• Patient has received chemotherapy within the last 4 weeks prior to first injection
• ECOG score greater than 1
• Estimated life expectancy of less than 6 months
• Pregnancy or breastfeeding
• Primary or secondary immunodeficiency, including immunosuppressive disease, and immunosuppressive doses of corticosteroids (e.g., prednisolone \> 7.5 mg per day) or other immunosuppressive medications including cyclosporine, azathioprine, interferons within the past 4 weeks prior to screening
• Positive serology for human immunodeficiency virus (HIV), hepatitis B or C
• Full dose anticoagulation or a history of bleeding diathesis or poorly controlled bleeding in the last month prior to screening

Sponsors & Collaborators

• Viralytics: lead

Study Sites (10)

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

St Mary's Medical Center

San Francisco, California, 94117, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Oncology Specialists, SC

Niles, Illinois, 60714, United States

Location

Investigative Clinical Research of Indiana

Indianapolis, Indiana, 46260, United States

Location

Atlantic Melanoma Center

Morristown, New Jersey, 07962, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75201, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Andtbacka RHI, Curti B, Daniels GA, Hallmeyer S, Whitman ED, Lutzky J, Spitler LE, Zhou K, Bommareddy PK, Grose M, Wang M, Wu C, Kaufman HL. Clinical Responses of Oncolytic Coxsackievirus A21 (V937) in Patients With Unresectable Melanoma. J Clin Oncol. 2021 Dec 1;39(34):3829-3838. doi: 10.1200/JCO.20.03246. Epub 2021 Aug 31.

  PMID: 34464163 DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Mark Grose
• Organization: Viralytics

Mark.Grose@Viralytics.com

1 647 821 7673

Study Officials

• Robert Andtbacka, MD

  Associate Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2010
• First Posted: October 25, 2010
• Study Start: December 29, 2011
• Primary Completion: April 6, 2016
• Study Completion: April 6, 2016
• Last Updated: July 5, 2019
• Results First Posted: May 15, 2017

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)