Clinical trial NCT01437605: Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Melanoma
Keywords: Resected
Skin
Stage IV
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Oncovir, Inc.
First posted: 2011-09-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Number of Participants With Adverse Events Related to Study Treatment
timeFrame: Beginning of Treatment to End of Follow Up - up to 5 years per participant
Secondary outcomes:
measure: Immunogenicity Per Treatment Arm
timeFrame: Beginning of Treatment to End of Follow Up - up to 5 years per participant
measure: Percentage of Participants With Relapse-Free Survival (RFS)
timeFrame: Beginning of Treatment to End of Follow Up - up to 2 years per participant
measure: Median Overall Survival (OS)
timeFrame: At 5 years
Other outcomes:
measure: Immunogenicity as Measured by T Cell Responses
timeFrame: Beginning of Treatment to End of Follow Up - up to 5 years per participant
measure: Correlation Between Gene Expression Profile and Treatment Clinical Activity
timeFrame: Beginning of Treatment to End of Follow Up - up to 5 years per participant
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Nikhil Khushalani, M.D.
role: PRINCIPAL_INVESTIGATOR
References: