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.
Active, not recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| TALIMOGENE LAHERPAREPVEC (TVEC) | Intralesional TALIMOGENE LAHERPAREPVEC with radiotherapy |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Intralesional TALIMOGENE LAHERPAREPVEC with radiotherapy | Experimental | 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. |
|
| Intralesional TALIMOGENE LAHERPAREPVEC without radiotherapy | Experimental | Patients will receive Talimogene Laherparepvec alone, as described above, without radiotherapy. |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | response |
| Time Frame: | 16 weeks |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
July 14, 2021
