Melanoma, Merkel Cell Carcinoma, Other Solid Tumors
Conditions
Keywords
T-VEC (Talimogene Laherparepvec), Radiotherapy, 16-224
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.
Interventions
RADIATIONHypofractionated Radiotherapy
Sponsors
Amgen
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy Patients will receive Talimogene Laherparepvec alone, as described above, without radiotherapy.
TALIMOGENE LAHERPAREPVEC (TVEC) | 9 |
| 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.
TALIMOGENE LAHERPAREPVEC (TVEC)
Hypofractionated Radiotherapy | 10 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression before RT | 0 | 1 |
Baseline characteristics
| Characteristic | Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy | Total | Intralesional TALIMOGENE LAHERPAREPVEC With Radiotherapy |
|---|---|---|---|
| Age, Continuous | 70 years | 65 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 17 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 15 Participants | 6 Participants |
| Region of Enrollment United States | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 9 | 9 / 10 |
| other Total, other adverse events | 9 / 9 | 10 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Best Response
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.
Time frame: 16 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy | Best Response | Complete Response | 1 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy | Best Response | Partial Response | 0 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy | Best Response | Stable Disease | 2 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy | Best Response | Progressive Disease | 6 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC With Radiotherapy | Best Response | Progressive Disease | 4 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC With Radiotherapy | Best Response | Complete Response | 1 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC With Radiotherapy | Best Response | Stable Disease | 5 Participants |
| Intralesional TALIMOGENE LAHERPAREPVEC With Radiotherapy | Best Response | Partial Response | 0 Participants |