CT-011 and p53 Genetic Vaccine for Advanced Solid Tumors

NCT01386502 | Withdrawn Phase 1

• 2 other identifiers: 11019811-C-0198
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• The p53 gene normally helps to stop cancer cells from growing. However, when the p53 gene is mutated or damaged, cancer cells may grow unchecked. Researchers have been working on a vaccine that will help the immune system recognize and destroy cells that have the p53 mutation and may be cancerous.
• CT-011 is another drug that may help the body's immune system to fight cancer. This drug blocks a chemical found on tumor cells that prevents the immune system from recognizing and destroying them. Research studies have shown that CT-011 slows the growth of tumors. By combining the p53 vaccine and CT-011, researchers hope to slow or stop tumor growth in people whose cancer that has not responded to standard treatments. Objectives: \- To test the safety and effectiveness of CT-011 and the p53 genetic vaccine to treat adults with solid tumors that have not responded to standard treatments. Eligibility: \- People at least 18 years of age who have solid tumors that have not responded to standard treatments. Design:
• Participants will be screened with a medical history and physical exam. They will also have blood tests and tumor imaging studies.
• Participants will receive the p53 vaccine as an injection in the arm or thigh.
• Two days after receiving the p53 vaccine, those in the study will receive CT-011 as an infusion over about 2 hours. Participants will be monitored during the infusion for any side effects.
• The combination of p53 vaccine and CT-011 will be repeated every 3 weeks (one cycle). Treatment will continue as long as the side effects are not severe and the tumor does not grow.
• Three weeks after the second dose of p53 vaccine and CT-011, participants will have a full physical exam. They will also have blood tests, and tumor imaging studies. This exam set will be repeated after every two cycles of p53 vaccine and CT-011.
• Participants will have regular follow-up visits for up to a year after stopping treatment.

Conditions

Breast Cancer; Colon Cancer; Pancreatic Cancer; Sarcoma; Ovarian Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (2)

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

• To determine the clinical efficacy of this combination.

Interventions

p53: 264-272 peptide BIOLOGICAL

CT-011 DRUG

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Solid malignancies with a histological confirmation of the original primary tumor via the pathology report for which no curative therapies are available.
• 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.
• 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).
• 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.
• Patients must be 18 years of age or older.
• Life expectancy of greater than 3 months.
• ECOG performance status of 0-1.
• ECG with no evidence of arrhythmia, conduction abnormality or ischemia.
• 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)

You may not qualify if:

• Concurrent therapy with any other investigational agent(s).
• 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 eligible.
• 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. .
• 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.)
• Patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH).
• 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.
• History of a second active malignancy in the last 2 years other than non-melanoma skin cancers or carcinoma in situ of the cervix.
• Patients with active infections requiring antibiotics.
• Patients with New York Heart Association stage 2 or greater heart failure, unstable angina or cardiac arrhythmias requiring therapy including atrial fibrillation.
• Pregnant women or nursing mothers are ineligible since the effect of this investigational treatment on the health of the fetus is not known.
• 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 eligible.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G, Elkum N, Alshabanah M, Bin Amer S, Tulbah A, Ajarim D, Al-Tweigeri T, Dermime S. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia. 2006 Mar;8(3):190-8. doi: 10.1593/neo.05733.

  PMID: 16611412 BACKGROUND

• Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, Sengupta S, Frank I, Parker AS, Zincke H, Blute ML, Sebo TJ, Cheville JC, Kwon ED. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006 Apr 1;66(7):3381-5. doi: 10.1158/0008-5472.CAN-05-4303.

  PMID: 16585157 BACKGROUND

• Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, Fujii S. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3360-5. doi: 10.1073/pnas.0611533104. Epub 2007 Feb 21.

  PMID: 17360651 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Sarcoma; Ovarian Neoplasms

Interventions

p53 peptide 264-272, human; pidilizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: July 1, 2011
• Study Start: June 15, 2011
• Study Completion: October 31, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-10-31

Locations

US (1)