A Study of T-VEC (Talimogene Laherparepvec) With or Without Radiotherapy for Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02819843

Collaborator

Amgen (Industry)

Enrollment

Locations

Arms

83.3

Anticipated Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this phase II clinical study is to test the good and bad effects of T-VEC (talimogene laherparepvec) with or without hypofractionated radiotherapy on people with melanoma, Merkel cell carcinoma, or other solid tumors with skin metastasis.

Condition or Disease	Intervention/Treatment	Phase
Melanoma Merkel Cell Carcinoma Other Solid Tumors	Drug: TALIMOGENE LAHERPAREPVEC (TVEC) Radiation: Hypofractionated Radiotherapy	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Randomized Trial of Intralesional Talimogene Laherparepvec (TALIMOGENE LAHERPAREPVEC) With or Without Radiotherapy for Cutaneous Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors

Actual Study Start Date :

Jun 21, 2016

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intralesional TALIMOGENE LAHERPAREPVEC with radiotherapy Patients will receive 3 radiotherapy treatments (one treatment every 3-5 days) during weeks 3 and 4. The first treatment will occur 6 (+/- 2) hours after the Talimogene Laherparepvec administration at week 3.Talimogene Laherparepvec will be administered at weeks 0, 3, 5, 7, 9, 11, 13 and 15. The first dose of Talimogene Laherparepvec will be 10^6 plaque forming units (PFU)/mL, followed three weeks later by a dose of 10^8 pfu/mL.	Drug: TALIMOGENE LAHERPAREPVEC (TVEC) Radiation: Hypofractionated Radiotherapy
Experimental: Intralesional TALIMOGENE LAHERPAREPVEC without radiotherapy Patients will receive Talimogene Laherparepvec alone, as described above, without radiotherapy.	Drug: TALIMOGENE LAHERPAREPVEC (TVEC)

Arm

Intervention/Treatment

Experimental: Intralesional TALIMOGENE LAHERPAREPVEC with radiotherapy

Patients will receive 3 radiotherapy treatments (one treatment every 3-5 days) during weeks 3 and 4. The first treatment will occur 6 (+/- 2) hours after the Talimogene Laherparepvec administration at week 3.Talimogene Laherparepvec will be administered at weeks 0, 3, 5, 7, 9, 11, 13 and 15. The first dose of Talimogene Laherparepvec will be 10^6 plaque forming units (PFU)/mL, followed three weeks later by a dose of 10^8 pfu/mL.

Drug: TALIMOGENE LAHERPAREPVEC (TVEC)

Radiation: Hypofractionated Radiotherapy

Experimental: Intralesional TALIMOGENE LAHERPAREPVEC without radiotherapy

Patients will receive Talimogene Laherparepvec alone, as described above, without radiotherapy.

Drug: TALIMOGENE LAHERPAREPVEC (TVEC)

Outcome Measures

Primary Outcome Measures

response [16 weeks]
Overall subject level response is defined as partial or complete (>50% or greater decrease in largest lesion) by the modified World Health Organization (mWHO) criteria, and will include measurements of tumor size by CT component of PET/CT, and clinically by digital photography.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Man or woman ≥ 18 years old
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 dimensionor exhibits radiotracer uptake consistent with metastasis on PET/CT
Adequate coagulation function (platelet count >50 k/mcL, international normalized ratio of < 1.5)
Resolution or stabilization of clinically significant adverse events from prior therapy
Able to provide valid written informed consent

Exclusion Criteria:

Active herpetic skin lesions or prior complications of 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
Receipt of another cancer therapy (targeted therapy, chemotherapy, investigational therapy, immunotherapy, radiotherapy or surgery) which is yielding an overall response (by response criteria in this study)

° Patients with stable or progressing disease (as determined by at least 2 consecutive assessments at 6-week interval) can continue to receive the same therapy during treatment as part of this protocol

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 (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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
2	Memoral Sloan Kettering Westchester	Harrison	New York	United States	10604
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065