Clinical Trials

Registration – Inclusion Criteria:

• Age ≥ 18 years.
• Newly diagnosed, recurrent, or previously treated in-transit metastatic melanoma (ITM) confined to a single limb.
• Regional involvement of the inguinal (lower limb) and axillary (upper limb) lymph nodes is permitted.
• One of the following must be true:
  • A visible superficial ITM, non-nodal lesion with longest diameter ≥ 0.2 cm in diameter as assessed using a ruler (e.g., skin nodules). Documentation by color photography, including a ruler is required;
  • A malignant regional lymph node with short axis > 1.0 cm as assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm);
  • A non-visible, non-nodal soft tissue mass of the involved extremity with longest diameter ≥1.0 cm as measured with CT scan, CT component of a PET/CT, or MRI.
• The following laboratory values obtained ≤ 15 days prior to registration:
  • Hemoglobin ≥ 8.0 g/dL;
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
  • Platelet count ≥ 75,000/mm^3;
  • Total bilirubin ≤ 1.5 × ULN;
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3.0 × ULN;
  • Serum creatinine ≤ 2.0 × ULN;
  • Calculated creatinine clearance ≥ 40 ml/min using the Cockcroft-Gault formula;
  • PT/INR/aPTT ≤ 1.5 × ULN
    OR if patient is receiving anticoagulant therapy INR or aPTT is within target range of therapy.
• ECOG Performance Status (PS) 0 or 1.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
• Persons able to become pregnant OR able to father a child must be willing to use an adequate method of contraception while on treatment and for 180 days (6 months) after last treatment dose on this study.
• Provide written informed consent.
• Willingness to provide mandatory blood specimens for correlative research.
• Willing to return to enrolling institution for 3-month follow-up (during the Active Monitoring Phase of the study).

Registration - Exclusion Criteria:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential who are unwilling to employ adequate contraception;
  • Persons expecting to conceive or father children during the study or within 180 days (6 months) after the last treatment on this study.
• Metastatic melanoma beyond in-transit metastases (ITM) and regional lymph nodes (LNs).
• ITM involving the hands and feet (not accessible to DoseConnect infusion).
• ITM NOT involving a limb (i.e., head, neck, or trunk).
• Prior radiation of ITM that are being evaluated as measurable lesions.
• Any of the following prior therapies:
  • Allogeneic hematopoietic stem cell transplantation (HSCT);
  • Solid organ transplantation.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• Active autoimmune disease requiring systemic treatment < 2 years prior to registration, documented history of severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents with use of disease modifying agents, corticosteroids, or immunosuppressive drugs.
  • NOTE: Exceptions are allowed for the following conditions:
  • Vitiligo;
  • Resolved childhood asthma/atopy;
  • Intermittent use of bronchodilators or inhaled steroids;
  • Daily steroids at dose of ≤ 10mg of prednisone (or equivalent);
  • Local steroid injections;
  • Stable hypothyroidism on replacement therapy;
  • Stable diabetes mellitus on therapy (with or without insulin);
  • Sjögren’s syndrome;
  • Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) which is not considered a form of systemic treatment and is allowed.
• Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection requiring systemic therapy;
  • Interstitial lung disease;
  • Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., Crohn’s disease or others);
  • Known history of hepatitis B (i.e., known positive HBV surface antigen (HBsAg) reactive);
  • Known active hepatitis C (i.e., positive for HCV RNA detected by PCR);
  • Known active tuberculosis (TB);
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris;
  • Unstable cardiac arrhythmia; or
  • Psychiatric illness/social situations that would limit compliance with study requirements (e.g., known substance abuse).
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• History of severe hypersensitivity reactions to other monoclonal antibodies or known hypersensitivity to the study intervention or its excipients, indocyanine green (ICG) dye or iodine.
• Prior history of Grade 4 immune related adverse event (irAE) with prior ICI therapy or failure to recover (< Grade 1) from immune-related adverse event(s) from prior ICI therapy.
• Any of the following therapies prior to registration:
  • Chemotherapy ≤ 21 days;
  • Immunotherapy ≤ 21 days;
  • Targeted therapies (e.g., dabrafenib) ≤ 21 days;
  • Other investigational agents ≤ 28 days;
  • Radiation therapy ≤ 14 days;
  • Minor surgical or interventional procedure ≤ 7 days, (biopsy of same limb for diagnosis allowed);
  • Major surgical procedure ≤ 21 days.

Eligibility last updated 12/17/21. Questions regarding updates should be directed to the study team contact.