Know Cancer

forgot password

Phase I Trial of Escalating Doses of Anti-PD1 Monoclonal Antibody (CT-011) in Combination With p53 Vaccine in Adults With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Breast Cancer, Colon Cancer, Pancreatic Cancer, Sarcoma, Ovarian Cancer

Thank you

Trial Information

Phase I Trial of Escalating Doses of Anti-PD1 Monoclonal Antibody (CT-011) in Combination With p53 Vaccine in Adults With Advanced Solid Tumors


- PD1 is an inhibitory receptor that belongs to CD28-B7 family.

- PD1 binds to two ligands PD-L1 and PD-L2 to down modulate T-cell immune responses.

- PD1 is expressed on T cells, B cells, and NK cells.

- The over expression of PD-1 ligand (PD-L1) in tumors is associated with an immune
suppression and poor prognosis.


- To determine the safety and tolerability of escalating doses of anti PD1 antibody
(CT-011) in combination with subcutaneous p53 vaccine.

- To determine the immune response to wt p53 (264-272) peptide.

- To determine the clinical efficacy of this combination.


- 18 years of age or older, not pregnant or nursing and not immunocompromised or having
an autoimmune disease.

- HLA-A2 haplotype.

- ECOG performance status of 0-1.

- Advanced solid tumors over expressing p53 protein with a histological confirmation of
the original primary tumor via the Pathology Laboratory, CCR , NCI.


- Single arm, pilot/phase I trial in patients receiving a fixed dose of vaccine in
combination with an escalating dose of CT-011.

- The vaccine will be administered subcutaneously every 3 weeks followed by CT-011 two
days after each vaccine until disease progression or toxicity.

- Patients will undergo blood draw or aphaeresis for immunologic assays prior to starting
treatment and after every second cycle.

- Patients will be assessed for overall safety, immunologic efficacy, tumor response
using RECIST criteria and survival.

- Patients will be followed for up to two years after the last vaccination for assessment
of safety and efficacy.

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
biopsy procedures.

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
physician immediately.

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
physiological abnormality.

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety and tolerability of escalating doses of anti PD1 antibody (CT-011) in combination with subcutaneous p53 vaccine.


United States: Federal Government

Study ID:




Start Date:

June 2011

Completion Date:

October 2011

Related Keywords:

  • Breast Cancer
  • Colon Cancer
  • Pancreatic Cancer
  • Sarcoma
  • Ovarian Cancer
  • Solid Tumors
  • Monoclonal Antibody
  • Peptide Vaccine
  • Toxicity
  • PD-1 ligand
  • Solid Tumor
  • Breast Cancer
  • Ovarian Cancer
  • Pancreatic Cancer
  • Colon Cancer
  • Sarcoma
  • Breast Neoplasms
  • Colonic Neoplasms
  • Ovarian Neoplasms
  • Pancreatic Neoplasms
  • Sarcoma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892