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Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma

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ClinicalTrials.gov Identifier: NCT02211131
Recruitment Status : Active, not recruiting
First Posted : August 7, 2014
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

Condition or disease Intervention/treatment Phase
Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma Drug: Talimogene Laherparepvec Procedure: Immediate surgical resection of melanoma lesion(s) Phase 2

Detailed Description:

This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

Arm 1: Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).

Arm 2: Immediate surgical resection of melanoma tumor lesion(s) Following surgery, adjuvant systemic therapy and/or radiotherapy may be administered at the investigator's discretion and per the institutional standard of care.

Subjects will be followed for safety approximately 30 (+15) days after surgery and for disease recurrence, subsequent anticancer therapy, and survival every 3 months (±30 days) for first 3 years after the end of the safety follow-up period and then every 6 months (±30 days) until death, subject withdraws full consent, or up to 5 years after the last subject is randomized.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Open-label Trial Assessing the Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Resectable, Stage IIIB to IVM1a Melanoma
Actual Study Start Date : February 3, 2015
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : April 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Talimogene Laherparepvec
Arm 1 Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).
Drug: Talimogene Laherparepvec
Talimogene laherparepvec will be administered by intralesional injection into the injectable cutaneous, subcutaneous, and nodal tumors initially at a dose of 10^6 plaque forming units (PFU)/mL at day 1 of week 1 followed by a dose of 10^8 PFU/mL at day 1 (±3 days) of week 4, 6, 8, 10 and 12 or until all injectable tumors have disappeared, or intolerance of study treatment or in the opinion of the investigator, immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first.

Surgery
Arm 2: Surgical resection of melanoma tumor lesion(s)
Procedure: Immediate surgical resection of melanoma lesion(s)
Surgical resection of melanoma tumor lesion(s) will be performed after randomization any time during weeks 1 to 6.




Primary Outcome Measures :
  1. Efficacy [ Time Frame: 24 months after last patient randomized ]
    Estimate the efficacy of neoadjuvant talimogene laherparepvec plus surgery versus surgery alone on recurrence-free survivial (RFS)


Secondary Outcome Measures :
  1. Efficacy [ Time Frame: Primary analysis for 2-year RFS will occur approximately 2 years after the end of randomisation. Additional analysis for 1-year and 3-year RFS and final analysis for 5-year RFS will occur approximately 1, 3 and 5 years after the end of randomization ]
    Estimate the efficacy of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on 1-year, 2-year, 3-year and 5-year RFS

  2. Efficacy [ Time Frame: 16 weeks after last patient randomized ]
    Estimate the efficacy of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on rate of histopathological tumor-free margin (R0) surgical resection

  3. Efficacy [ Time Frame: 16 weeks after last patient randomized ]
    Estimate the effect of neoadjuvant talimogene laherparepvec on rate of pathological complete response (pCR)

  4. Efficacy [ Time Frame: 24 months after last patient randomized ]
    Estimate the effect of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on local recurrence-free survival (LRFS) and distant metastases-free survival (DMFS)

  5. Efficacy [ Time Frame: Primary analysis for 2 year OS will occur approximately 2 years after the end of randomisation. Additional analysis for 1-year and 3-year OS and final analysis for 5-year OS will occur approximately 1, 3 and 5 years after the end of randomization ]
    Estimate the effect of neoadjuvant talimogene laherparepvec plus surgery compared to surgery alone on 1-year, 2-year, 3-year, 5-year and overall survival (OS)

  6. Overall Response [ Time Frame: 16 weeks after last patient randomized ]
    Estimate response to neoadjuvant talimogene laherparepvec overall and seperately in injected and uninjected lesions during treatment (Arm 1 only)

  7. Safety [ Time Frame: 16 weeks after 40tth, 75th and last patient randomized ]
    Evaluate the safety of neoadjuvant talimogene laherparepvec plus surgery commpared to surgery alone



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of stage IIIB, IIIC or IVM1a melanoma eligible for complete surgical resection.
  • Prior systemic, regional and radiation anticancer therapies for melanoma must have been completed at least 3 months prior to randomization.
  • Subject must have measurable disease and must be a candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must have a serum lactate dehydrogenase (LDH) ≤ 1.0 X upper limit of normal and adequate hematologic, hepatic, renal, and coagulation organ function- Other criteria may apply

Exclusion Criteria:

  • Subject must not have primary ocular or mucosal melanoma, or history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia).
  • Subject must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease.
  • Subject must not have evidence of clinically significant immunosuppression or active herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
  • Subject known to have acute or chronic active hepatitis B, hepatitis C, or human immunodeficiency virus infection will also be excluded.
  • Subject must not have been treated previously with talimogene laherparepvec or tumor vaccine.

Other criteria may apply


Information from the National Library of Medicine

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): NCT02211131


  Show 46 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02211131     History of Changes
Other Study ID Numbers: 20110266
2014-001146-13 ( EudraCT Number )
First Posted: August 7, 2014    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas