Phase I Trial of Escalating Doses of Anti-PD1 Monoclonal Antibody (CT-011) in Combination With p53 Vaccine in Adults With Advanced Solid Tumors
- INCLUSION CRITERIA:
1. Solid malignancies with a histological confirmation of the original primary
tumor via the pathology report for which no curative therapies are available.
2. Patients must have disease progression after at least one prior first line
disease-appropriate therapy, or be unable to tolerate or declined to receive
first line therapy.
3. No chemotherapy or radiation therapy or systemic steroids for at least 4 weeks
prior to starting vaccination. No immunotherapy (including monoclonal
antibodies) within 4 weeks prior to start of vaccine. Patients should have
recovered from all acute toxicities of previous treatment (excluding alopecia).
4. Patients must have tumors over expressing p53 protein as assessed by
immunohistochemistry, as determined by positive staining of tumor sample when
compared to negative controls. The immunohistochemical staining will be
performed in the Pathology Laboratory, CCR, NCI on fresh or archival tissue and
will be supervised by Dr. Merino. The criteria used to determine overexpression
will be that used in the Pathology Laboratory: Ten fields will be evaluated at
40 times magnification and if > 25% of cells stain positive, the tumor will be
categorized as an overexpressor. Fresh tissue from a new biopsy will only be
collected for IHC staining if the tumor is easily accessible and does not pose
greater than minimal risk. A separate procedure consent will be required for all
5. Patients must be 18 years of age or older.
6. Life expectancy of greater than 3 months.
7. ECOG performance status of 0-1.
8. ECG with no evidence of arrhythmia, conduction abnormality or ischemia.
9. Patients must have organ and marrow function as defined below:
i. Leukocytes greater than or equal to 2,500/mcL
ii. Lymphocytes greater than or equal to 800/mcL
iii. ANC greater than or equal to 1000/mcL
iv. Platelets greater than or equal to 100,000/mcL
v. Total Bilirubin less than or equal 2mg/dL
vi. AST (SGOT)/ALT (SGPT) less than or equal to 1.5 times the institutional
upper limit of normal (ULN)
vii. Creatinine less than or equal to 2mg/dL
10. Patients must have HLA-A0201.
11. Patients must be willing to travel to the NIH Clinical Center for treatment and
follow up visits.
12. Willing to use effective birth control measures: Since the effects of P53
vaccine and CT-011 on the developing human fetus are unknown and potentially
harmful, women of child-bearing potential and men with partners of childbearing
potential must agree to use adequate contraception (hormonal or double barrier
method of birth control or complete abstinence) prior to study entry and for the
duration of study participation and for one month after the last dose of
investigational agent. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating
13. Patients must understand and sign an informed consent document that explains the
neoplastic nature of his/her disease, the procedures to be followed, the
experimental nature of the treatment, alternative treatments, and potential
risks and toxicities.
1. Concurrent therapy with any other investigational agent(s).
2. Patients with known brain metastases are excluded from this clinical trial because of
their poor prognosis and frequent development of progressive neurological dysfunction
that would confound the evaluation of neurological and other adverse events. Patients
with treated brain metastases which have been stable for 6 months or longer will be
3. Patients who are immunocompromised (HIV positive) or with active Hepatitis B or C;
HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with CT-011 or p53. .
4. Patients who have underlying immune deficiency or history of autoimmune disease
(including but not limited to SLE, rheumatoid arthritis, multiple sclerosis,
inflammatory bowel disease, regional enteritis or other diseases known or presumed to
be of autoimmune origin.)
5. Patients being chronically treated with immunosuppressive drugs such as cyclosporin,
adrenocorticotropic hormone (ACTH).
6. Concurrent use of systemic steroids except physiologic doses for systemic steroid
replacement or local therapy. Physiologic doses are defined as daily systemic therapy
used to replace endogenous steroids because of HPA axis dysfunction or other
7. History of a second active malignancy in the last 2 years other than non-melanoma
skin cancers or carcinoma in situ of the cervix.
8. Patients with active infections requiring antibiotics.
9. Patients with New York Heart Association stage 2 or greater heart failure, unstable
angina or cardiac arrhythmias requiring therapy including atrial fibrillation.
10. Pregnant women or nursing mothers are ineligible since the effect of this
investigational treatment on the health of the fetus is not known.
11. If, in the opinion of the Principal or Associate Investigators, it is not in the best
medical interest of the patient to enter this study, the patient will not be
12. Patients with history of chronic radiation injury/inflammation due to the risk of
perforation in the event of autoimmune inflammation, or history of chronic diarrhea
due to previous treatments or surgery.