Clinical Trial: Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase II Study of T-VEC Followed by T-VEC + Nivolumab in Refractory T Cell and NK Cell Lymphomas, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Other Rare Skin Tumors

Brief Summary: This phase II trial studies how well talimogene laherparepvec works and nivolumab in treating patients with lymphomas that do not responded to treatment or non-melanoma skin cancers that have spread to other places in the body 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. Monoclonal antibodies, such as nivolumab, may block a protein needed by tumor cells to grow and spread. Giving talimogene laherparepvec and nivolumab may work better in treating patients with lymphomas or non-melanoma skin cancers.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the frequency of patients responding (response rate) to talimogene laherparepvec (T-VEC) monotherapy.

SECONDARY OBJECTIVES:

I. To determine the local response rate to T-VEC in injected tumors. II. To determine the response rate to T-VEC + 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) on day 1. Patients without response at week 12, may also receive nivolumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 21 or 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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 30, 2016
Date Started: August 4, 2017
Date Completion: January 31, 2019
Last Updated: May 25, 2017
Last Verified: May 2017