Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01740297
First received: November 14, 2012
Last updated: February 23, 2015
Last verified: February 2015

November 14, 2012
February 23, 2015
February 2013
May 2016   (final data collection date for primary outcome measure)
  • 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) in subjects with previously untreated, unresected, stages IIIB to IV melanoma
  • Efficacy [ Time Frame: 24 months following last subject randomized ] [ Designated as safety issue: No ]
    Phase 2: Evaluate the efficacy as assessed by confirmed objective response rate (ORR) of treatment with talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in subjects with unresected, stages IIIB to IV melanoma.
  • Safety and Tolerability [ Time Frame: 24 months 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)
Complete list of historical versions of study NCT01740297 on ClinicalTrials.gov Archive Site
  • 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: Best Overall Response (BOR), Disease Control Rate (DCR), Ordinal Categorical Response Score, Deep Response Rate, Durable Response Rate (DRR), Duration of Response (DOR), Time to response (TTR), Progression free survival (PFS), resection rate, Overall Survival (OS), 1-year survival rate, 2-year survival rate
  • 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
Not Provided
Not Provided
 
Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma
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 Unresected, Stage IIIB-IV Melanoma

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • 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, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurs first.
    Other Name: Talimogene laherparepvec plus Yervoy
  • Drug: Ipilimumab
    Ipilimumab administered intravenously on Day 1 of Week 1, 4, 7, and 10 for a total of 4 infusions.
    Other Name: Yervoy
  • Experimental: Phase 1b and Phase 2 Arm 1
    Talimogene laherparepvec plus ipilimumab
    Intervention: Drug: Talimogene laherparepvec plus ipilimumab
  • Active Comparator: Phase 2 Arm 2
    Ipilimumab
    Intervention: Drug: Ipilimumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
219
November 2017
May 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed diagnosis of malignant melanoma.
  • Stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c disease that is not suitable for surgical resection
  • Phase1: 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.
  • Phase 2: Either treatment naïve or received only one line of systemic anticancer therapy if BRAF wild-type or up to two lines of systemic anticancer therapy including one BRAF inhibitor-containing regimen if BRAF mutant. Treatments given in an adjuvant setting (eg, interferon, radiotherapy, isolated limb perfusion, or investigational agents) are not considered as prior lines of therapy. No prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines are allowed, even if given in the adjuvant setting.
  • Phase 2: Subjects treated with prior ipilimumab must have had PR, CR, or at least 6 months of stable disease followed by disease progression.
  • Phase 2: Subjects previously treated with anti-PD1 or anti-CTLA-4 antibodies must not have discontinued therapy due to any treatment-related adverse events including immune-related adverse events. Prior treatment-related adverse events should also be fully resolved and not requiring treatment for at least 28 days prior to randomization.
  • 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)
  • Phase 1b: History or evidence of central nervous system (CNS) metastases
  • Phase 2: Clinically active cerebral melanoma metastases. Subjects with up to 3 cerebral metastases, and neurological performance status of 0 may be enrolled,provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or Gamma knife therapy, with no evidence of progression, and have not required steroids, for at least 2 months prior to enrollment.
  • 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
  • Phase 1b: Prior talimogene laherparepvec, ipilimumab, other Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitors, programmed death-1 (PD-1) inhibitors, or tumor vaccine
  • Phase 2: Prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines
  • Currently receiving or less than 28 days since ending systemic anticancer treatment for unresected stage IIIB to IV melanoma
Both
18 Years and older
No
Contact: Amgen Call Center 866-572-6436
United States
 
NCT01740297
20110264
Yes
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP