Clinical Trial 19381

Cancer Type:
Interventions:DTIC (Dacarbazine); Dacarbazine; Not Applicable; PV-10; Talimogene Laherparepvec (OncoVEX); Talimogene laherparepvec 10^6 PFU (Talimogene Laherparepvec); Talimogene laherparepvec 10^8 PFU (Talimogene Laherparepvec); Temodal (Temozolomide); Temozolomide

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Jonathan Zager

Overview

Study Title

PV-10 Intralesional Injection vs Systemic Chemotherapy or Intralesional Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma

Summary

The purpose of this study is to see if an investigational drug called PV-10 can help people with melanoma.

Objective

Primary Objective: The primary objective of this randomized controlled trial (RCT) is to assess the effectiveness of intralesional (IL) PV-10 compared to the Investigators choice of systemic chemotherapy or intralesional oncolytic viral therapy in treating locally advanced cutaneous melanoma. Effectiveness will be assessed by comparison of progression-free survival (PFS) between all intent-to-treat (ITT) subjects in the two study treatment arms. Secondary Objectives: This study will also include assessment and comparison of the two study treatment arms with respect to: Complete response rate (CRR). Duration of complete response. Overall survival (OS). Safety and tolerability.

Inclusion Criteria

  • Age 18 years or older, male or female
  • Histologically or cytologically confirmed melanoma
  • Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous melanoma metastases (i.e., AJCC Stage IIIB, IIIC or Stage IV M1a with no active nodal metastases)
  • At least 1 measurable Target Lesion that can be accurately measured by calipers or computed tomography (CT) consisting of: at least one cutaneous lesion (each lesion ≥ 10 mm in longest diameter or up to 5 lesions having a sum of longest diameters ≥ 10 mm); and/or; at least one subcutaneous lesion (each lesion ≥ 10 mm in longest diameter by CT); where Target Lesions should be at least 10 mm from any other lesion.
  • No lesion > 50 mm in longest diameter; and no more than 50 lesions
  • Calculated required PV-10 dose ≤ 15 mL (based on total tumor burden)
  • Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2
  • Not a candidate for treatment with an immune checkpoint inhibitor (e.g., failed or did not tolerate prior therapy, or due to co-morbidities, pre-existing autoimmune disease, drug unavailability or standard of care)
  • Not a candidate for targeted therapy with BRAF or combined BRAF/MEK inhibitors (e.g., failed or did not tolerate prior therapy, BRAF V600 wild-type or due to drug unavailability or standard of care)
  • Clinical Laboratories: Adequate hepatic, renal and bone marrow function
  • Lactate dehydrogenase (LDH) ≤ 2 times the upper limit of normal (ULN).
  • Thyroid function abnormality ≤ Grade 2
  • Candidate for at least one comparator drug: Participants must be candidates for at least one of the designated comparator drugs

  • Exclusion Criteria

  • Presence or history of visceral melanoma metastasis
  • Presence of active nodal metastases (e.g., radiologic or clinical evidence of current nodal disease)
  • Presence of more than 50 melanoma lesions
  • Radiation therapy to any Study Lesion within 6 weeks of initial study treatment.
  • Chemotherapy or other systemic cancer therapy within 4 weeks of initial study treatment (6 weeks for nitrosoureas or mitomycin), or regional chemotherapy (limb infusion or perfusion) within 12 weeks of initial study treatment
  • Immunotherapy for cancer within 4 weeks of initial study treatment
  • Local treatment (e.g., surgery, cryotherapy, laser ablation) to any Study Lesion within 4 weeks of initial study treatment
  • Anti-tumor vaccine therapy within 6 weeks of initial study treatment.
  • Investigational agents within 4 weeks of initial study treatment.
  • Concurrent or Intercurrent Illness:
  • Impaired wound healing or other extremity complications due to diabetes mellitus in subjects whose Study Lesions are located in an extremity
  • Severe peripheral vascular disease in potential participants whose Study Lesions are located in an extremity
  • Significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise the subject's safety or compliance or interfere with interpretation of study results.
  • Uncontrolled thyroid disease or cystic fibrosis
  • Clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders
  • Females who are pregnant or lactating
  • Females who have positive serum pregnancy test taken within 14 days of study treatment
  • Females of child-bearing potential who are unwilling to use highly effective contraception according to study for the duration of study treatment
  • Contraindication for all comparators: Potential participants with contraindications to all of the designated comparator drugs