November 30, 2016
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December 1, 2016
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March 21, 2024
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September 27, 2017
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June 1, 2024 (Final data collection date for primary outcome measure)
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Best overall response rate to talimogene laherparepvec alone as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 1 year ] 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 RR = 4/17 or 23.5%), T-VEC would be considered promising in that tumor type. Between-arm comparisons will not be performed
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- 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.
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- Best overall response rate to talimogene laherparepvec and nivolumab combination therapy as assessed by RECIST version 1.1 [ Time Frame: Up to 1 year ]
- Durable response rate defined as complete response or partial response lasting >= 6 months [ Time Frame: Up to 1 year ]
- Frequency of curative surgery (unresectable lesion becomes resectable) [ Time Frame: Up to 1 year ]
- Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to week 24 ]
- Overall survival [ Time Frame: At 1 year ]
- Overall survival [ Time Frame: At 2 years ]
- 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 ]
- Response rate by cancer type assessed by RECIST version 1.1 [ Time Frame: Up to 1 year ]
- Response rate of injected lesions assessed by RECIST version 1.1 [ Time Frame: Up to 1 year ]
- Response rate of non-injected lesions assessed by RECIST version 1.1 [ Time Frame: Up to 1 year ]
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- 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.
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- 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 % 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 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.
- 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.
- Change in 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.
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Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
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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
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This phase II trial studies how well talimogene laherparepvec and nivolumab work in treating patients with lymphomas that do not responded to treatment (refractory) or non-melanoma skin cancers that have spread to other places in the body (advanced) or do not responded to treatment. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and nivolumab may work better compared to usual treatments in treating patients with lymphomas or non-melanoma skin cancers.
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PRIMARY OBJECTIVE:
I. To determine the frequency of patients responding (response rate) to talimogene laherparepvec monotherapy.
SECONDARY OBJECTIVES:
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.
OUTLINE:
Patients receive talimogene laherparepvec intratumorally (IT) and nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or positron emission tomography (PET)/CT scan on study. Patients also undergo blood sample collection and biopsies on study.
After completion of study treatment, patients are followed up every 12 weeks for 3 years.
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Interventional
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Phase 2
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Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Adenoid Cystic Skin Carcinoma
- Adnexal Carcinoma
- Anaplastic Large Cell Lymphoma, ALK-Negative
- Anaplastic Large Cell Lymphoma, ALK-Positive
- Apocrine Carcinoma
- Cylindrocarcinoma
- Digital Papillary Adenocarcinoma
- Endocrine Mucin-Producing Sweat Gland Carcinoma
- Extramammary Paget Disease
- Extraocular Cutaneous Sebaceous Carcinoma
- Hidradenocarcinoma
- Keratoacanthoma
- Malignant Sweat Gland Neoplasm
- Merkel Cell Carcinoma
- Microcystic Adnexal Carcinoma
- NK-Cell Lymphoma, Unclassifiable
- Papillary Adenocarcinoma
- Porocarcinoma
- Primary Cutaneous Mucinous Carcinoma
- Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
- Recurrent T-Cell Non-Hodgkin Lymphoma
- Refractory Anaplastic Large Cell Lymphoma
- Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
- Refractory Merkel Cell Carcinoma
- Refractory Mycosis Fungoides
- Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
- Refractory Skin Squamous Cell Carcinoma
- 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
- Squamoid Eccrine Ductal Carcinoma
- Squamous Cell Carcinoma of Unknown Primary
- Sweat Gland Carcinoma
- Trichilemmal Carcinoma
- Vulvar Squamous Cell Carcinoma
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Experimental: Treatment (talimogene laherparepvec, nivolumab)
Patients receive talimogene laherparepvec IT and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo, CT scan or PET/CT on study. Patients also undergo blood sample collection and biopsies on study.
Interventions:
- Procedure: Biopsy
- Procedure: Biospecimen Collection
- Procedure: Computed Tomography
- Other: Laboratory Biomarker Analysis
- Biological: Nivolumab
- Procedure: Positron Emission Mammography
- Biological: Talimogene Laherparepvec
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Not Provided
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Active, not recruiting
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68
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Same as current
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June 1, 2024
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June 1, 2024 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Patients must have histologic or cytologic diagnosis of non-melanoma skin cancer (NMSC) or lymphomas other than B-cell lymphomas; as both of those terms are categories rather than specific diagnoses, specific guidance on eligible tumor types is provided below
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PART I (before February 2020 amendment): Included tumor types
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PART II (after February 2020 amendment):
- The Merkel cell carcinoma (MCC)-2 cohort will include patients with MCC
- The squamous cell carcinoma (SCC)-2 cohort will include patients with SCC
- PART I (before February 2020 amendment): Patients with T cell and natural killer (NK) cell lymphomas must be refractory to, be intolerant of, have relapsed following, or have refused all standard life-prolonging therapies
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PART I (before February 2020 amendment): Patients with non-melanoma skin cancers (NMSC) must have advanced or refractory tumors
- Advanced/unresectable is defined by at least 1 of the following criteria: tumors 2 cm or more, tumors considered unresectable, tumors invading deep tissues such as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes and/or distant sites
- Refractory is defined by persistent or recurrent tumor despite prior therapy consisting of at least 1 of the following: surgery, radiation therapy, intralesional therapy, topical therapy, or systemic therapy
- PART I (before February 2020 amendment): Subjects must have at least 1 cutaneous, subcutaneous, or nodal lesion that is suitable for intralesional injection, with or without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc) are not eligible for injection because the area cannot be properly contained with an occlusive dressing
- PART I (before February 2020 amendment): Subjects must have radiographically or clinically measurable disease, defined as at least one lesion that is >= 10 mm in diameter in at least 1 dimension, or an aggregate of lesions that measures >= 10 mm in diameter in at least 1 dimension
- PART I (before February 2020 amendment): Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions
- PART I (before February 2020 amendment): Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- PART I (before February 2020 amendment): Absolute neutrophil count (ANC) >= 1.2 x 10^9/L
- PART I (before February 2020 amendment): Hemoglobin >= 9 g/dL without transfusion in the preceding 7 days
- PART I (before February 2020 amendment): Platelets >= 75 x 10^9/L
- PART I (before February 2020 amendment): Serum total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome with a total bilirubin < 3.0 mg/dL)
- PART I (before February 2020 amendment): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN
- PART I (before February 2020 amendment): Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
- PART I (before February 2020 amendment): Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x institutional ULN, unless the subject is on anticoagulant therapy; (if the subject is receiving anticoagulant therapy, PT, and activated PTT [aPTT] must be within therapeutic range of intended use of anticoagulants)
- PART I (before February 2020 amendment): Talimogene laherparepvec, nivolumab and other therapeutic agents used in this trial may cause fetal harm when administered to a pregnant woman; women of child-bearing potential (WOCBP) and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence from heterosexual intercourse) prior to study entry, during the study participation, and for 7 months after the last dose of the drug; WOCBP must have a negative serum pregnancy test within 14 days prior to randomization; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men must agree to use adequate contraception prior to study entry, during the study participation and for 7 months after the last dose of the drug
- PART I (before February 2020 amendment): Ability to understand and the willingness to sign a written informed consent document
- PART II (after February 2020 amendment): Subjects in expansion cohorts MCC-2 and SCC-2 must have a diagnosis of MCC or SCC, respectively
- PART II (after February 2020 amendment): Subjects must have refractory disease, defined as evidence of progressive disease despite prior therapy with a PD-1 or PD-L1 blocking antibody (avelumab, pembrolizumab, nivolumab, cemiplimab, etc.); progression must have occurred during PD-1 or PD-L1 directed therapy or within 6 months of the last dose of PD-1 or PD-L1 directed therapy
- PART II (after February 2020 amendment): Subjects must have at least 1 cutaneous, subcutaneous, or nodal lesion that is suitable for intralesional injection, with or without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc) are not eligible for injection because the area cannot be properly contained with an occlusive dressing
- PART II (after February 2020 amendment): Subjects must have radiographically or clinically measurable disease, defined as at least one lesion that is >= 10 mm in diameter in at least 1 dimension, or an aggregate of lesions that measures >= 10 mm in diameter in at least 1 dimension
- PART II (after February 2020 amendment): Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions
- PART II (after February 2020 amendment): ECOG performance status =< 2 (Karnofsky >= 60%)
- PART II (after February 2020 amendment): Absolute neutrophil count (ANC) >= 1.2 x 10^9/L
- PART II (after February 2020 amendment): Hemoglobin >= 9 g/dL without transfusion in the preceding 7 days
- PART II: P (after February 2020 amendment): Platelets >= 75 x 10^9/L
- PART II (after February 2020 amendment): Serum total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Patients with Gilbert's Syndrome with a total bilirubin < 3.0 mg/dL.)
- PART II (after February 2020 amendment): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN
- PART II (after February 2020 amendment): Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
- PART II (after February 2020 amendment): Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x institutional ULN, unless the subject is on anticoagulant therapy; (if the subject is receiving anticoagulant therapy, PT, and aPTT must be within therapeutic range of intended use of anticoagulants)
- PART II (after February 2020 amendment): Talimogene laherparepvec, nivolumab and other therapeutic agents used in this trial may cause fetal harm when administered to a pregnant woman; women of child-bearing potential (WOCBP) and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence from heterosexual intercourse) prior to study entry, during the study participation, and for 7 months after the last dose of the drug; WOCBP must have a negative serum pregnancy test within 14 days prior to randomization; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men must agree to use adequate contraception prior to study entry, during the study participation and for 7 months after the last dose of the drug
- PART II (after February 2020 amendment): Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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United States
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NCT02978625
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NCI-2016-01804 NCI-2016-01804 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CINJ #091701 10057 ( Other Identifier: Dana-Farber - Harvard Cancer Center LAO ) 10057 ( Other Identifier: CTEP ) UM1CA186709 ( U.S. NIH Grant/Contract ) UM1CA186716 ( U.S. NIH Grant/Contract )
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No
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Not Provided
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National Cancer Institute (NCI)
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Same as current
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National Cancer Institute (NCI)
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Same as current
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Not Provided
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Principal Investigator: |
Ann (Annie) W Silk |
Dana-Farber - Harvard Cancer Center LAO |
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National Cancer Institute (NCI)
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March 2024
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