Safety Study of CADI-05 in Patients With Advanced Stage Melanoma
Safety Study of CADI-05 in Patients With Advanced Stage Melanoma
This study examines the safety of treating patients with advanced stage melanoma with the
 vaccine CADI-05. In addition, preliminary data regarding the clinical response and immune
 response will be collected.
Because there are no highly effective treatment options for patients with advanced,
 unresectable melanoma, participation in clinical trials of novel therapies is frequently the
 best therapeutic alternative. CADI-05 is a promising agent for two reasons. First, patients
 with advanced melanoma frequently have disturbing symptoms such as anorexia with associated
 weight loss, fatigue, and chemotherapy-associated side effects such as nausea and vomiting.
 CADI-05 not only has a very low side effect profile, but it actually improves such symptoms.
 Second, melanomas are generally immunogenic, and sometimes patients mount significant of
 immune responses to cause spontaneous regression of tumors. High-dose interleukin-2, a
 relatively toxic therapy that stimulates the immune system, causes long-term regression in
 stage IV melanoma in a small percentage of patients. In addition, when combined with adoptive
 immunotherapy, response rates as high as 50% have been observed. Therefore, induction of
 potent antitumor immune responses in melanoma can be a highly effective therapeutic modality.
 Because CADI-05 has potent immunostimulatory effects and an excellent side effect profile, it
 is a very attractive option for treatment of stage IV melanoma patients. Preliminary data
 from ongoing preclinical studies in a murine melanoma model have shown that CADI-05 has
 significant biological activity in metastatic melanoma (G. Robertson, unpublished data).

 Although it is possible that CADI-05 as a single agent will have activity in advanced
 melanoma, it may also be useful in conjunction with other systemic agents or as an adjuvant
 in conjunction with immunotherapy regimens. In addition, previous human trials suggest that
 CADI-05 may be helpful in symptom control and improvement of quality of life in patients with
 advanced melanoma. In spite of the promising data from a number of preclinical and clinical
 studies of this agent, no U.S. studies of the effects of CADI-05 in cancer patients have been
 performed. Therefore, the present research study proposes to evaluate the safety of CADI-05
 treatment in advanced melanoma. In addition, preliminary data regarding the clinical response
 rate and immune response will be collected.
Inclusion Criteria:

 -  At least 18 years of age

 -  Ability to understand and the willingness to sign a written informed consent document

 -  Subject must have a pathologic diagnosis malignant melanoma (stage III or IV).

 -  Subject must have at least one of the following:

 1. Melanoma that was previously treated with at least one complete or partial course
 of therapy for melanoma with either a poor to no response or evidence of disease
 progression;

 2. Melanoma that cannot be treated with first-line therapies because of medical
 comorbidities/risk of toxicity; or

 3. Melanoma that has not been treated with first-line therapies because of patient
 refusal.

 -  If melanoma is possibly resectable, the melanoma must have recurred despite at least
 two attempts at resection.

 -  The subject must have measurable disease, as defined by the presence of at least one
 measurable lesion, defined as having longest diameter greater than or equal to 20 mm
 by conventional measurement techniques (e.g., measurement of evaluable cutaneous
 metastases) or greater than or equal to 20 mm by imaging studies.

 -  Subject must have an ECOG performance status of 0, 1, or 2.

 -  Subject must have the ability to understand and provide informed consent that fulfills
 Institutional Review Board guidelines. Alternatively, if the subject is mentally
 incompetent for medical decision-making, a parent, legal guardian, or power of
 attorney has the ability to understand and provide informed consent that fulfills
 Institutional Review Board guidelines.

 -  Subject must be able to comply with office visits as required by the protocol.

 -  The effects of Investigational product on the developing human fetus is at the
 recommended therapeutic dose are unknown. For this reason, women of childbearing
 potential and men must agree to use adequate contraception (hormonal or barrier method
 of birth control; abstinence) prior to study entry and for the duration of study
 participation. Should a woman become pregnant or suspect she is pregnant while
 participating in this study, she should inform her treating physician immediately.

 Exclusion Criteria:

 -  Subjects with medical co-morbidities, which in the judgment of the investigator, place
 them at an unacceptable level of risk for participation in this study.

 -  Pregnant women, since the prenatal effects of CADI-05 have not been characterized.

 -  Subjects with HIV, AIDS, or chronic immunosuppression for organ transplantation.

 -  Subjects who are unable to comply with office visits as required by this protocol or
 would suffer great hardship by participating in the study.

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to agents used in the study.

 -  Clinically significant active infection.