Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
GlaxoSmithKline
Oncovir, Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01437605
First received: September 19, 2011
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

The overall purpose of this research study is to find a better way to treat melanoma.

The goals of this study are:

  1. To measure the side effects of and find out how well patients tolerate the recMAGE-A3 + AS15 ASCI (MAGE-A3 ASCI) treatment with or without the Poly IC:LC
  2. To see how well the patient's immune system responds to the MAGE-A3 ASCI treatment with or without the Poly IC:LC
  3. To measure the rate of return of the patient's tumor after the MAGE-A3 ASCI treatment with or without the Poly IC:LC
  4. To measure the rate of return of the patient's tumor in two groups of patients: one group positive for the gene signature, and the other group not positive for the gene signature in their tumor after the MAGE-A3 ASCI treatment with or without the Poly IC:LC.

Condition Intervention Phase
Melanoma
Drug: MAGE-A3 ASCI injections without Poly IC:LC
Drug: MAGE-A3 ASCI injections with Poly IC:LC
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: A Randomized Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC in Patients With Resected MAGE-A3 Positive, Stage IV Melanoma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: Beginning of Treatment to End of Follow Up - up to 5 years per participant ] [ Designated as safety issue: Yes ]
    Toxicity and tolerability in the two study arms (recMAGE-A3 + AS15 ASCI and recMAGE-A3 + AS15 ASCI in combination with Poly IC:LC) defined by the adverse events and serious adverse events. Adverse events (AEs), including abnormal laboratory values, will be graded according to the Common Toxicity Criteria for Adverse Effects (CTCAE) Version 4.0 and coded to the preferred term (PT) level using the Medical Dictionary for Regulatory Activities (MedDRA) dictionary.

  • Number of Participants With Immune Response [ Time Frame: Beginning of Treatment to End of Follow Up - up to 5 years per participant ] [ Designated as safety issue: No ]
    Immunogenicity in the two study arms (recMAGE-A3 + AS15 ASCI and recMAGE-A3 + AS15 ASCI in combination with Poly IC:LC) defined by antibodies serum titer (such as anti-MAGE-A3).


Secondary Outcome Measures:
  • Immunogenicity as Measured by T Cell Responses [ Time Frame: Beginning of Treatment to End of Follow Up - up to 5 years per participant ] [ Designated as safety issue: No ]
    Immunogenicity as measured by T cell responses directed against MAGE-A3 antigen.

  • Number of Participants With Relapse-Free Survival (RFS) [ Time Frame: Beginning of Treatment to End of Follow Up - up to 5 years per participant ] [ Designated as safety issue: No ]
    RFS, defined as the time from randomization to the date of first relapse of melanoma or of death, whichever comes first. The analysis of RFS will be performed on the overall study Total Treated population. The primary analysis will be based on the adjusted Cox regression model.

  • Number of Participants With Overall Survival (OS) [ Time Frame: Beginning of Treatment to End of Follow Up - up to 5 years per participant ] [ Designated as safety issue: No ]
    OS defined as the interval from randomization to the date of death, irrespective of the cause of death; patients still alive will be censored at the date of the last assessment. The primary analysis will be based on the adjusted Cox regression model.

  • Correlation Between Gene Expression Profile and Treatment Clinical Activity [ Time Frame: Beginning of Treatment to End of Follow Up - up to 5 years per participant ] [ Designated as safety issue: No ]
    A potential correlation between gene expression profile and treatment clinical activity (RFS) in both study arms (recMAGE-A3 + AS15 ASCI and recMAGE-A3 + AS15 ASCI in combination with Poly IC:LC).


Estimated Enrollment: 44
Study Start Date: October 2011
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: recMAGE-A3 + AS15
ASCI injections without Poly IC:LC
Drug: MAGE-A3 ASCI injections without Poly IC:LC
MAGE-A3 ASCI injections without Poly IC:LC as outlined in Detailed Description
Other Names:
  • Recombinant MAGE-A3 protein
  • AS15 adjuvant
Active Comparator: B: recMAGE-A3 + AS15 + Poly IC:LC
ASCI injections with Poly IC:LC
Drug: MAGE-A3 ASCI injections with Poly IC:LC
MAGE-A3 ASCI injections with Poly IC:LC as outlined in Detailed Description
Other Names:
  • Recombinant MAGE-A3 protein
  • AS15 adjuvant
  • Hiltonol
  • NSC 301463

Detailed Description:

In the first year, participants may receive up to 8 injections given in the following order:

  1. 5 ASCI injections with or without Poly IC:LC with a 3-week interval between each.
  2. 3 ASCI injections with or without Poly IC:LC with a 3-month interval between each.

    During years 2 through 3, participants may receive up to 5 ASCI injections with or without Poly IC:LC given in the following order:

  3. During year 2, ASCI injections with or without Poly IC:LC will be given every 3 months for a total of up to 3 injections.
  4. During year 3, ASCI injections with or without Poly IC:LC will continue to be given every 3 months for a total of up to 2 more injections.
  Eligibility

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

Inclusion Criteria:

  • Written informed consent for the study will be obtained prior to the performance of MAGE-A3 expression screening on resected tumor tissue or any other protocol-specific procedure.
  • Male or female patient with histologically proven and completely resected stage IV cutaneous or mucosal melanoma. In terms of the American Joint Committee on Cancer (AJCC) classification [AJCC, 2009], this means that patients with resected M1a-b-c (stage IV) disease may be enrolled.
  • The patient must have been surgically rendered free of disease no more than 12 weeks before the randomization.
  • Patient is equal to or greater than 18 years old at the time of signing the informed consent form.
  • The patient's tumor shows expression of the MAGE-A3 gene, as determined by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis on paraffin imbedded tumor tissue (FFPE). In all patients in whom it can be obtained, a frozen portion of the resected tumor will be analyzed for gene profiling.
  • The patient has fully recovered from surgery.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization.
  • The patient must have adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria: Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10^9/L, Platelet count equal to or greater than 75 x 10^9/L, Serum creatinine equal to or less than 1.5 times the Upper Limit of Normal (ULN), Total bilirubin equal to or less than 1.5 times the ULN, Transaminase (ALT - AST) equal to or less than 2.5 times the ULN
  • If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to randomization, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series.
  • Men must also agree to use an adequate method of contraception.
  • In the opinion of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

  • The patient has an ocular melanoma.
  • The patient has in-transit metastases.
  • The patient has been treated or is scheduled to be treated with an adjuvant anticancer therapy after the metastasectomy that qualifies the patient for inclusion in the present trial.
  • One prior systemic treatment with an immunomodulator (i.e., interferon, vaccine and/or anti-CTLA-4) after a previous surgery is permitted, provided that the last dose has been administered at least 45 days before randomization in the present trial.
  • Previous radiotherapy is permitted, provided that the treatment has been completed before the surgery that qualifies the patient for participation in the present trial.
  • The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents. The use of prednisone, or equivalent, at a dose of < 0.125 mg/kg/day (absolute maximum 10 mg/day) or topical steroids is permitted.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study treatment within 30 days preceding the randomization or planned use during the study period.
  • The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
  • The patient has a family history of congenital or hereditary immunodeficiency.
  • The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
  • History of allergic disease or reactions likely to be exacerbated by any component of the treatments.
  • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
  • The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  • The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
  • The patient has an uncontrolled bleeding disorder.
  • For female patients: the patient is pregnant or lactating.
  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: NCT01437605

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
GlaxoSmithKline
Oncovir, Inc.
Investigators
Principal Investigator: Jeffrey S. Weber, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01437605     History of Changes
Other Study ID Numbers: MCC-16545
Study First Received: September 19, 2011
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Resected
Skin
Stage IV

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Poly I-C
Anti-Infective Agents
Antiviral Agents
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014