Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
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|ClinicalTrials.gov Identifier: NCT02978625|
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : April 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|Adenoid Cystic Carcinoma Adnexal Carcinoma Apocrine Carcinoma Eccrine Porocarcinoma Extraocular Cutaneous Sebaceous Carcinoma Hidradenocarcinoma Keratoacanthoma Malignant Sweat Gland Neoplasm Merkel Cell Carcinoma Microcystic Adnexal Carcinoma NK-Cell Lymphoma, Unclassifiable Non-Melanomatous Lesion Paget Disease Papillary Adenocarcinoma Primary Cutaneous Mucinous Carcinoma Refractory Anaplastic Large Cell Lymphoma Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Refractory Mycosis Fungoides Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Refractory T-Cell Non-Hodgkin Lymphoma Sezary Syndrome Signet Ring Cell Carcinoma Skin Basal Cell Carcinoma Skin Basosquamous Cell Carcinoma Skin Squamous Cell Carcinoma Spiradenocarcinoma Squamous Cell Carcinoma of Unknown Primary Origin Stage III Skin Cancer Stage IV Skin Cancer Sweat Gland Carcinoma Trichilemmocarcinoma Vulvar Squamous Cell Carcinoma||Other: Laboratory Biomarker Analysis Biological: Nivolumab Biological: Talimogene Laherparepvec||Phase 2|
I. To determine the frequency of patients responding (response rate) to talimogene laherparepvec monotherapy.
I. To determine the local response rate to talimogene laherparepvec in injected tumors.
II. To determine the response rate to talimogene laherparepvec + nivolumab (NIVO).
III. To identify potential pre-treatment and on-treatment correlative biomarkers of local and systemic immune response.
Patients receive talimogene laherparepvec intratumorally (IT) on day 1. Patients without response at week 12, may also receive nivolumab intravenously (IV) over 60 minutes on day 1. Cycles repeat every 21 for course 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Talimogene Laherparepvec Followed by Talimogene Laherparepvec + Nivolumab in Refractory T Cell and NK Cell Lymphomas, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Other Rare Skin Tumors|
|Actual Study Start Date :||September 18, 2017|
|Estimated Primary Completion Date :||January 1, 2020|
|Estimated Study Completion Date :||January 1, 2020|
Experimental: Treatment (talimogene laherparepvec, nivolumab)
Patients receive talimogene laherparepvec IT on day 1. Patients without response at week 12, may also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 21 days for course 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Biological: Talimogene Laherparepvec
- Best overall response rate to talimogene laherparepvec alone [ Time Frame: Up to 1 year ]Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Arm assignment is based on tumor type: Merkel cell carcinoma, squamous cell carcinoma, other non-melanoma skin cancers, and refractory T cell lymphomas and NK cell lymphomas. If at least 4 responses were observed in an arm (observed response rate [RR] = 4/17 or 23.5%), talimogene laherparepvec (T-VEC) would be considered promising in that tumor type. Between-arm comparisons will not be performed
- Best overall response rate to talimogene laherparepvec and nivolumab combination therapy [ Time Frame: Up to 1 year ]Will be assessed by RECIST version 1.1.
- Durable response rate [ Time Frame: Up to 1 year ]Will be defined as complete response or partial response lasting >= 6 months.
- Response rate by cancer type [ Time Frame: Up to 1 year ]Will be assessed by RECIST version 1.1.
- Response rate of injected lesions [ Time Frame: Up to 1 year ]Will be assessed by RECIST version 1.1.
- Response rate of non-injected lesions [ Time Frame: Up to 1 year ]Will be assessed by RECIST version 1.1.
- Frequency of curative surgery (unresectable lesion becomes resectable) [ Time Frame: Up to 1 year ]
- Progression free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed at 1 year ]
- Progression free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed at 2 years ]
- Overall survival [ Time Frame: At 1 year ]
- Overall survival [ Time Frame: At 2 years ]
- Incidence of adverse events [ Time Frame: Up to week 24 ]Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Change in herpes simplex virus (HSV) serostatus assessed in blood specimens [ Time Frame: Baseline to week 6 ]Will be analyzed using descriptive statistics. A test of proportions will be performed.
- Biomarker analysis of %PD-L1, flow cytometry for HVEM, NECTIN1/2, and IDO, tryptophan and L-kynurenine, cytokine levels, Nanostring, number of non-synonymous mutations, and % T-cell receptor (TCR) clonality [ Time Frame: Up to 1 year ]Will be analyzed using descriptive statistics. Logistic regression of response rate on the variable will be performed.
- Biomarker analysis of necrosis and Nanostring [ Time Frame: Up to 1 year ]Will be analyzed using descriptive statistics. Logistic regression of response rate on the variable will be performed.
- Biomarker analysis of herpes simplex virus (HSV) status, Merkel cell polyomavirus status, and PD-L1 status [ Time Frame: Up to 1 year ]Will be analyzed using descriptive statistics. Test of proportions and logistic regression will be performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02978625
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|Principal Investigator:||Ann (Annie) W Silk||Rutgers University - Cancer Institute of New Jersey LAO|