Safety Study of a Cell Penetrating Peptide (p28) to Treat Solid Tumors That Resist Standard Methods of Treatment

NCT00914914 | Completed Phase 1 DMC

• 4 other identifiers: CDGTI-p28-001IND 777542008-0213PAF 2009-03370
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety of an experimental drug (p28) as a treatment for certain advanced cancers which express a protein called p53 and which have not responded to prior treatment.

Conditions

Refractory Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Clinical and laboratory adverse reactions will be closely monitored by periodic physical and laboratory examination.

  32 weeks

• Grade 3 non-hematologic or Grade 4 hematologic toxicity will also define the Maximum Feasible Dose (MFD).

  32 weeks

Secondary Outcomes (2)

• Reduction in the size of measurable tumors using the RECIST criteria and, if possible, demonstration of p28 localization and biopsy of tumor.

  32 weeks

• Calculate peak (serum) concentration of p28 and compare with any sign of toxicity and response.

  32 weeks

Study Arms (1)

p28 Phase I Safety

EXPERIMENTAL

A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3þ3 dose escalation design.

Drug: p28

Interventions

p28 DRUG

p28 will be dissolved in normal saline and infused intravenously into the patient over 15-30 minutes.

Also known as: azurin

p28 Phase I Safety

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically proven solid tumor disease with documentation of measurable metastatic disease as defined by RECIST.
• The term refractory solid tumor signifies patients with metastatic solid tumors who have failed all standard therapy or for whom no standard therapy exists.
• In patients with refractory solid tumors, a pretreatment biopsy (either of the original primary or metastatic deposit) must show p53 (wild-type and to an extent mutant) expression by means of immunocytochemistry.
• Patients must have distant metastases or unresectable local disease, but a projected life expectancy of at least 6 months.
• Patients must have signed an informed consent.
• This study is confined to adults of both sexes, age 18 or older.
• Patients must have no medical problems that would pose an undue risk or that would limit full compliance with the study.
• A minimum of 4 weeks must have elapsed since the completion of prior therapy, including hormonal therapy, chemotherapy, radiation therapy, immunotherapy, oral tyrosine kinase inhibitors and monoclonal antibodies.
• Adequate baseline organ function assessed by the following laboratory values within 30 days prior to study entry:
• Granulocyte count \>1,500/mm3, hematocrit \>30%, and platelets \>100,000/mm3.
• Calculated creatinine clearance \>50ml/min.
• Adequate liver function with SGOT, SGPT, LDH, and alkaline phosphatase \<3 x the upper limit of normal; serum bilirubin \<2.0 mg/dl.
• PT and PTT not more than 1.5 times the upper limit of normal.
• Adequate cardiac and pulmonary function. Patients with decreased LVEF or PFTs will be evaluated by a cardiologist or pulmonary physician prior to enrollment of this protocol.

You may not qualify if:

• Patients who are undergoing chemotherapy or immunotherapy, i.e., cytokines
• Patients with refractory solid tumors whose primary tumor or metastatic deposits do not express p53 (null) will not be eligible.
• Patients with serious additional illness, including HIV, hepatitis, or untreated active infection.
• Patients with any underlying conditions that would contraindicate therapy with the study agent.
• Patients with a history of prior malignancy in the past five years other than the current problem for which he/she is being considered for this trial (patients with prior history of basal cell carcinoma or squamous cell skin cancer are eligible).
• Patients with any other serious medical, i.e., cardiovascular, uncontrolled diabetes (insulin resistant), or psychiatric illness that would prevent informed consent will not be eligible to participate in the study.
• Patients who are either pregnant or lactating (all patients of childbearing potential will receive a pregnancy test within 2 days of study initiation).
• Brain Metastases, current or past (unless treated at least one year prior to enrollment).

Sponsors & Collaborators

• Dr. Tapas K. Das Gupta: lead

Study Sites (1)

University of Illinois at Chicago Department of Surgical Oncology

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Warso MA, Richards JM, Mehta D, Christov K, Schaeffer C, Rae Bressler L, Yamada T, Majumdar D, Kennedy SA, Beattie CW, Das Gupta TK. A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours. Br J Cancer. 2013 Mar 19;108(5):1061-70. doi: 10.1038/bjc.2013.74. Epub 2013 Feb 28.

  PMID: 23449360 BACKGROUND

MeSH Terms

Interventions

Interleukin-27; Azurin

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Bacterial Proteins; Metalloproteins

Study Officials

• Michael A Warso, M.D.

  University of Illinois Department of Surgical Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-founder

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 5, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: June 1, 2011
• Last Updated: October 28, 2014

Record last verified: 2014-10

Locations

US (1)