CT-011 and p53 Genetic Vaccine for Advanced Solid Tumors

Breast Cancer Clinical Trial

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

Status Withdrawn

Clinical Trial 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.

Clinical Trial Description

Background:

• 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.

Objectives:

• 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.

Eligibility:

• 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.

Design:

• 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. ;

Related Conditions & MeSH terms

• Breast Cancer
• Colon Cancer
• Colonic Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms
• Sarcoma

• NCT number: NCT01386502
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Phase: Phase 1
• Start date: June 15, 2011
• Completion date: October 31, 2011