Talimogene Laherparepvec with or without Hypofractionated Radiation Therapy in Treating Patients with Metastatic Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors

Status: Active

Description

This randomized phase II trial studies the side effects of talimogene laherparepvec and to see how well it works with or without hypofractionated radiation therapy in treating patients with skin melanoma, Merkel cell carcinoma, or other solid tumors that have spread to places not suitable for surgical removal. Drugs used in the immunotherapy, such as talimogene laherparepvec, may stimulate the body's immune system to fight tumor cells. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if giving talimogene laherparepvec with or without hypofractionated radiation therapy will work better in treating patients with cutaneous melanoma, Merkel cell carcinoma, or solid tumors.

Eligibility Criteria

Inclusion Criteria

  • Life expectancy > 4 months
  • Histopathologically confirmed melanoma, Merkel cell carcinoma or other solid tumor malignancy
  • Cutaneous, subcutaneous soft tissue, or superficial lymphatic metastasis not suitable for surgical resection
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Cutaneous, subcutaneous soft tissue, or superficial lymphatic metastasis that is amenable to injection and irradiation and > 10 mm in longest dimension * Cutaneous metastasis in a region of previous radiation therapy is amenable to radiation therapy as part of this protocol if at least 6 months has elapsed since prior radiotherapy and the dose of radiotherapy previously administered did not exceed an equivalent dose of 60 Gy in 2 Gy equivalent fractions at the skin surface (using linear-quadratic modeling with alpha/beta = 11.5)
  • Metastasis that is > 10 mm in longest dimension or exhibits radiotracer uptake consistent with metastasis on positron emission tomography/computed tomography (PET/CT)
  • Platelet count > 50 k/mcL
  • International normalized ratio of < 1.5
  • Completion of other cancer therapy (targeted therapy, chemotherapy, investigational therapy, immunotherapy, radiotherapy, surgery) 14 days prior to first dose of protocol therapy * For patients with breast cancer only: ** May continue ongoing antiestrogen therapy (for example, aromatase inhibitor) ** May continue ongoing human epidermal growth factor receptor (Her)2 directed therapy (for example, trastuzumab)
  • Resolution or stabilization of clinically significant adverse events from prior therapy (completed at least 14 days prior to first dose of talimogene laherparepvec [TVEC])
  • Able to provide valid written informed consent

Exclusion Criteria

  • Active herpetic skin lesions or prior complications of herpes simplex virus (HSV)-1 infection (such as herpetic keratitis, herpetic encephalitis)
  • Receipt of a therapeutic anticoagulant
  • Receipt of live vaccine within 28 days of planned first dose of TVEC
  • History of symptomatic autoimmune disease (such as lupus, scleroderma, Crohn’s disease, ulcerative colitis) requiring systemic treatment (for example corticosteroids or immunosuppressants); replacement therapy (for example, thyroxine, insulin) is not considered a systemic treatment
  • History of high grade (Common Terminology Criteria for Adverse Events [CTCAE] >= grade 3) immune mediated adverse event from prior cancer immunotherapy
  • History of CTCAE >= grade 2 immune mediated endocrinopathy from prior cancer immunotherapy
  • Intermittent or chronic use of oral or intravenous antiherpetic drug (such as acyclovir)
  • Active or chronic hepatitis B or C infection * Previously infected with evidence of immunity and no evidence of active hepatitis is not an exclusion criterion
  • Known human immunodeficiency virus (HIV) infection
  • Known leukemia or lymphoma
  • Common variable immunodeficiency
  • Patients requiring chronic high dose immunosuppressants including steroids (prednisone daily equivalent of >= 10 mg)
  • Known severe congenital or acquired cellular or humoral immunodeficient or immunocompromised patients
  • High likelihood of protocol non-compliance (in opinion of investigator)
  • Woman of childbearing potential unwilling to use effective contraception during protocol treatment and for 3 months after last dose of talimogene laherparepvec
  • Woman of childbearing potential that is pregnant or breast-feeding, or planning to become pregnant or breast-feed during protocol treatment and for 3 months after last dose of talimogene laherparepvec

Locations & Contacts

New Jersey

Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Christopher Andrew Barker
Phone: 212-639-8168

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Christopher Andrew Barker
Phone: 212-639-8168
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Christopher Andrew Barker
Phone: 212-639-8168

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the systemic efficacy of talimogene laherparepvec with or without radiotherapy in patients with cutaneous metastases from melanoma, Merkel cell carcinoma, or other solid tumor malignancy.

SECONDARY OBJECTIVES:

I. To assess the clinical efficacy of talimogene laherparepvec with or without radiotherapy in patients with cutaneous metastases from melanoma, Merkel cell carcinoma, or other solid tumor malignancy.

II. To assess the safety of talimogene laherparepvec with or without radiotherapy in patients with cutaneous metastases from melanoma, Merkel cell carcinoma, or other solid tumor malignancy as measured by the frequency of adverse events (grade 2-5 adverse events).

III. To evaluate the patient reported quality of life following talimogene laherparepvec with or without radiotherapy in patients with cutaneous metastases from melanoma, Merkel cell carcinoma, or other solid tumor malignancies treated with talimogene laherparepvec with or without hypofractionated radiotherapy.

IV. To assess the duration of response (DOR) in patients achieving a partial or complete response.

V. To assess the time to response onset in following talimogene laherparepvec with or without radiotherapy.

VI. To estimate progression free and overall survival in patients receiving talimogene laherparepvec with or without radiotherapy for cutaneous metastases from melanoma and Merkel cell carcinoma.

TERTIARY OBJECTIVES:

I. To characterize the immunologic response to talimogene laherparepvec with or without radiotherapy in patients with cutaneous metastases from melanoma, Merkel cell carcinoma, or other solid malignancies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive talimogene laherparepvec intralesionally at weeks 0, 3, 5, 7, 9, 11, 13, and 15 for a total of 8 doses. After 6 hours of talimogene laherparepvec injection at week 3, patients undergo hypofractionated radiation therapy every 3-6 days during weeks 3-4 for a total of 3 doses.

ARM B: Patients receive talimogene laherparepvec intralesionally at weeks 0, 3, 5, 7, 9, 11, 13, and 15 for a total of 8 doses.

After completion of study treatment, patients are followed up at week 20.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Christopher Andrew Barker

Trial IDs

Primary ID 16-224
Secondary IDs NCI-2016-01215
Clinicaltrials.gov ID NCT02819843