| Eligibility |
Inclusion Criteria:
1. Subjects with unresectable American Joint Committee on Cancer (AJCC) stage IIIB or
stage IIIC melanoma, or stage IV metastatic melanoma that have clinical or
radiological evidence of disease. Subjects may have had cutaneous, uveal, mucosal
primary melanoma, or an unknown primary melanoma. Staging must be confirmed by
cytological or histological examination. Staging of cutaneous melanoma will be based
on the revised AJCC staging system
2. Ability to provide written informed consent/assent for the trial.
3. =18 years of age
4. A subject may be naïve for immunotherapy agents or have received interferon-alpha,
ipilimumab or other cytotoxic T lymphocyte antigen (CTLA)-4 antibody, Programmed
death-1 (PD-1) antibody (or anti-PD-L1 antibody), interleukin-2, or prior cancer
vaccines other than the 6MHP vaccine. Patients who have received a PD-1/PD-L1 antibody
may be enrolled in either of the following settings:
1. A patient who has experienced progression of melanoma during that therapy or
after having completed that therapy,
2. A patient who fails to experience an objective clinical response (partial
response or complete response by RECIST 1.1 criteria) after either 12 weeks of
continuous anti-PD1 antibody or anti-CTLA4/anti-PD1 combination therapy, and is a
candidate to receive pembrolizumab therapy
5. Measurable disease based on RECIST 1.1.
Subjects will be required to have radiological studies to define radiologically
evident disease. Required studies include:
- Chest CT scan,
- Abdominal and pelvic CT scan, and
- Head CT scan or MRI Positron emission tomography (PET)/CT fusion scan may replace
scans of the chest, abdomen, and pelvis.
6. Subjects who have metastatic melanoma available for biopsy pretreatment and on day 22
must consent to having those biopsies. These metastases may be in nodes, skin, soft
tissue, liver, or other sites that can be accessed safely by needle biopsy, incisional
or excisional biopsy, with or without image guidance. The lesions to be biopsied must
be specified at study enrollment and not included as target lesions for RECIST
calculations. In instances where disease that is accessible to biopsy is limited,
archival tissue specimens collected after a subject's last systemic therapy may be
used for baseline measures.
Subjects must have measurable disease in addition to the lesion(s) to be biopsied.
7. Subjects who have had brain metastases will be eligible if all of the following are
true:
- Each brain metastasis must have been completely removed by surgery or each
unresected brain metastasis must have been treated with stereotactic
radiosurgery.
- There has been no evident growth of any brain metastasis since the most recent
treatment
- No brain metastasis is > 2 cm in diameter at the time of registration.
- Neurologic symptoms have returned to baseline,
- There is no evidence of new or enlarging brain metastases,
- Subjects are not using steroids for at least 7 days prior to registration.
8. The most recent surgical resections or gamma-knife therapy for malignant melanoma must
have been completed = 1 week prior to registration.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10. Adequate organ function.
11. Two intact (undissected) axillary and/or inguinal lymph node basins.
Exclusion Criteria
1. Is currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks of the first dose of
treatment.
2. Is currently receiving Interferon (e.g. Intron-A®), growth factors (e.g. Procrit®,
Aranesp®, Neulasta®), or interleukins (e.g. Proleukin®), or has received these agents
within 4 weeks of the first dose of treatment.
3. Is currently receiving nitrosureas or has received this therapy within the preceding 6
weeks of first dose of treatment.
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment with the following exceptions (which are permitted):
- replacement steroid doses in patients with adrenal or pituitary insufficiency
- Intra-articular steroid injections
- Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) at low doses (less than 500
mcg fluticasone per day, or equivalent)
- Topical and nasal corticosteroids
- Non-steroidal anti-inflammatory drugs
5. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
recovered (i.e. = Grade 1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or external beam
radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e.,
= Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
therapy.
7. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include carcinoma in situ of the breast (DCIS or LCIS), basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer
that has undergone potentially curative therapy.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.
9. Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents. Exceptions to this criterion
include:
- Subjects with vitiligo or other depigmenting illness.
- Resolved childhood asthma/atopy
- Intermittent use of bronchodilators or local steroid injections
- Hypothyroidism stable on hormone replacement or Sjogren's syndrome
- The presence of laboratory evidence of autoimmune disease (e.g. positive ANA
titer) without symptoms
- Mild arthritis requiring NSAID medications
10. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
15. Is HIV positive or has evidence of active Hepatitis C virus (testing to be done within
6 months of study entry) or active Hepatitis B virus.
16. Has received a live vaccine or allergy desensitization injections within 30 days prior
to the first dose of trial treatment.
17. Has known or suspected allergies to any component of the vaccine.
18. Has been vaccinated previously with any of the synthetic peptides included in this
protocol.
19. Is classified according to the New York Heart Association classification as having
Class III or IV heart disease (Appendix 12.5).
20. Has uncontrolled diabetes, defined as having a HGBA1C > 7.5%.
21. Has a body weight < 110 pounds (without clothes) at enrollment, due to the amount and
frequency with which blood will be drawn.
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