Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01740297
First received: November 14, 2012
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

Phase 1b of the study will evaluate the safety of talimogene laherparepvec in combination with ipilimumab. Phase 2 is a randomized study that will evaluate the safety and efficacy of talimogene laherparepvec in combination with ipilimumab versus ipilumumab alone. Talimogene laherparepvec will be administered by intratumor injection, and ipilimumab will be administered by intravenous infusion for a total of 4 infusions. Subjects will be treated with talimogene laherparepvec until complete response, all injectable tumors have disappeared, disease progression per a modified Immune-Related Response Criteria (irRC), or intolerance of study treatment.


Condition Intervention Phase
Melanoma
Drug: Talimogene laherparepvec plus ipilimumab
Drug: Ipilimumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1b/2, Multicenter, Open-label Trial to Evaluate the Safety and Efficacy of Talimogene Laherparepvec and Ipilimumab Compared to Ipilimumab Alone in Subjects With Previously Untreated, Unresected, Stage IIIb-IV Melanoma

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 12 weeks following last subject enrolled ] [ Designated as safety issue: Yes ]
    Phase 1b: Determine the safety and tolerability of talimogene laherparepvec in combination with ipilimumab as assessed by incidence of dose-limiting toxicities (DLT)

  • Efficacy [ Time Frame: 24 months following last subject randomized ] [ Designated as safety issue: No ]
    Phase 2: Estimate the efficacy of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone as assessed by overall survival (OS)


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 24 months following last subject enrolled ] [ Designated as safety issue: No ]
    Phase 1b: Objective Response Rate (ORR)

  • Safety [ Time Frame: 24 months following last subject enrolled ] [ Designated as safety issue: Yes ]
    Phase 1b and Phase 2: Incidence of all AEs, grade 3 or greater AEs, Serious adverse events, events requiring discontinuation of study drug, local effects on tumor, clinically significant laboratory changes, and clinically significant changes in vital signs

  • Efficacy [ Time Frame: 24 months following last subject randomized ] [ Designated as safety issue: No ]
    Phase 2: Objective Response Rate, Time to Response (TTR), Duration of Response (DOR), Progression free survival (PFS), resection rate, 1-year survival rate, 2-year survival rate


Estimated Enrollment: 149
Study Start Date: February 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b and Phase 2 Arm 1
Talimogene laherparepvec plus ipilimumab
Drug: Talimogene laherparepvec plus ipilimumab
Talimogene laherparepvec administered by intratumoral injection on Day 1 of Week 1, Day 1 of Week 4, then every two weeks thereafter. Ipilimumab administered intravenously on Day 1 of Week 6, Week 9, Week 12, and Week 15 for a total of 4 infusions. Subjects will be treated wtih talimogene laherparepvec until complete response, all injectable tumors have disappeared, disease progression per the modified irRC, or intolerance of study treatment, whichever occurs first.
Other Name: Talimogene laherparepvec plus Yervoy
Active Comparator: Phase 2 Arm 2
Ipilimumab
Drug: Ipilimumab
Ipilimumab administered intravenously on Day 1 of Week 1, 4, 7, and 10 for a total of 4 infusions.
Other Name: Yervoy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of malignant melanoma.
  • Stage IIIb, IIIc, IVM1a, IVM1b, or IVM1c disease that is not suitable for surgical resection
  • Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIb to IV melanoma.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate hematologic, hepatic, renal, and coagulation functions

Exclusion Criteria:

  • Primary uveal or mucosal melanoma
  • History or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia)
  • History or evidence of central nervous system (CNS) metastases
  • History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease) or other symptomatic autoimmune disease
  • History of or plan for splenectomy or splenic irradiation
  • Active herpetic skin lesions or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis).
  • Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
  • Known human immunodeficiency virus (HIV) disease
  • Known acute or chronic hepatitis B or hepatitis C infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01740297

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 21 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01740297     History of Changes
Other Study ID Numbers: 20110264
Study First Received: November 14, 2012
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
melanoma, talimogene laherparepvec, ipilimumab, metastatic melanoma, melanoma, immunotherapy, unresectable melanoma, oncolytic immunotherapy,

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
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014