Patient case: 74-year-old female with melanoma; genetic feature: no tumor infiltrating lymphocytes

Clinical trial: A Phase I/II Trial to Evaluate a Peptide Vaccine Plus Ipilimumab in Patients With Melanoma

Summary: This study evaluates whether it is safe to administer a peptide vaccine with ipilimumab. This study will also evaluate the effects of the combination of the peptide vaccine and ipilimumab on the immune system. The investigators will monitor these effects by performing tests in the laboratory on participants' blood, a lymph node, and tumor samples.


Eligibility: Inclusion Criteria:
  -  Participants with measurable stage IIIB, IIIC, or IV melanoma that have clinical or radiological evidence of disease. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. The diagnosis of stage IIIB-IV melanoma must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on the revised AJCC staging system. Participants must be eligible to be treated with ipilimumab based on clinician judgment within standard of care.
  -  Participants 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 PET/CT fusion scan may replace scans of the chest, abdomen, and pelvis.
  -  Participants who have metastatic melanoma available for biopsy pre-treatment and on day 22 must consent to having those biopsies. Metastases may be in nodes, skin, soft tissue, liver, or other sites that can be accessed by core needle biopsy, or incisional or excisional biopsy, with or without image guidance. The lesion(s) must be large enough to enable biopsy of at least 0.1 cm3 of tumor tissue (ideally 0.3 cm3 or more) in 5 core biopsies (ideally 14-16 gauge, but 18 gauge is acceptable) or incisional/excisional biopsies at both time points. Biopsies may be taken from a single lesion or multiple lesions at each of the time points depending on the size of each lesion. Different lesions may sampled at each time point. It is acceptable to perform a biopsy pretreatment, and then to perform an excision at day 22, even under general anesthesia if needed. The lesions to be biopsied must be specified at study enrollment and not included as target lesions for RECIST calculations. There must be measurable disease in addition to the lesion(s) to be biopsied. Up to 15 participants whose metastases are not available for biopsy may be enrolled in the first stage of enrollment, and up to 17 participants whose metastases are not available for biopsy may be enrolled in the second stage of enrollment.
  -  Participants who have had brain metastases will be eligible if all of the following are true:
  -  The total number of brain metastases ever ≤ 3,
  -  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.
  -  The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week prior to registration.
  -  ECOG performance status of 0 or 1
  -  Ability and willingness to give informed consent
  -  Laboratory parameters as follows:
  -  ANC ≥ 1000/mm3
  -  Platelets ≥100,000/mm3
  -  Hgb ≥ 9 g/dL
  -  Hgb-A1C ≤ 7.5%
  -  AST and ALT ≤ 2.5 x upper limits of normal (ULN)
  -  Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4x ULN is allowed).
  -  Alkaline phosphatase ≤ 2.5 x ULN
  -  Creatinine ≤ 1.5 x ULN
  -  Age 18 years or older at registration.
  -  Participants must have at least two intact (undissected) axillary and/or inguinal lymph node basins
  Exclusion Criteria:
  -  Participants who have received the following medications or treatments at any time within 4 weeks of registration:
  -  Chemotherapy
  -  Interferon (e.g. Intron-A®)
  -  Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week prior to registration)
  -  Allergy desensitization injections
  -  High doses of systemic corticosteroids, with the following qualifications and exceptions:
  -  Daily doses of 10 mg predisone (or equivalent) per day administered parenterally or orally are not allowed in patients with normal adrenal and pituitary function.
  -  In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed.
  -  Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent).
  -  Topical and nasal corticosteroids are acceptable.
  -  Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
  -  Interleukins (e.g. Proleukin®)
  -  Any investigational medication
  -  Targeted therapies specific for mutated BRAF or for MEK
  -  HIV positivity or evidence of active Hepatitis C virus (testing to be done within 6 months of study entry).
  -  Participants who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks
  -  Participants who are currently receiving a checkpoint molecule blockade therapy, or who have received this therapy within the preceding 6 weeks. Participants may not have previously been treated with a CTLA4 blocking antibody.
  -  Participants with known or suspected allergies to any component of the vaccine.
  -  Participants may not have been vaccinated previously with any of the synthetic peptides included in this protocol. Participants who have received vaccinations containing agents other than the synthetic peptides included in this protocol and have recurred during or after administration of the vaccine will be eligible to enroll 12 weeks following their last vaccination.
  -  Pregnancy. Female participants of childbearing potential must have a negative pregnancy test (urinary or serum beta-HCG) obtained within 2 weeks prior to registration. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. This is consistent with existing standards of practice for vaccine and chemotherapy protocols.
  -  Female participants must not be breastfeeding
  -  Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
  -  Participants classified according to the New York Heart Association classification as having Class III or IV heart disease.
  Participants with uncontrolled diabetes, defined as having a HGBA1C> 7.5%.
  -  Participants must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded. The following will not be exclusionary:
  -  The presence of laboratory evidence of autoimmune disease (e.g. positive ANA titer) without symptoms
  -  Clinical evidence of vitiligo
  -  Other forms of depigmenting illness
  -  Mild arthritis requiring NSAID medications
  -  A history of immune-related adverse events with immune therapy, if they have resolved completely.
  -  Participants who have another cancer diagnosis, except that the following diagnoses will be allowed:
  -  squamous cell cancer of the skin without known metastasis
  -  basal cell cancer of the skin without known metastasis
  -  carcinoma in situ of the breast (DCIS or LCIS)
  -  carcinoma in situ of the cervix
  -  any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 5 years
  -  Participants with known addiction to alcohol or drugs who are actively taking those agents, or participants with recent (within 1 year) or ongoing illicit IV drug use.
  -  Body weight < 110 pounds at registration, due to the amount and frequency with which blood will be drawn.

Relevance to patient case: possibly relevant