A Phase I Trial of p28 (Cell Penetrating Peptide) in the Treatment of Refractory Solid Tumors
18 Years
N/A
Both
Refractory Solid Tumors
Trial Information
A Phase I Trial of p28 (Cell Penetrating Peptide) in the Treatment of Refractory Solid Tumors
The drug used in this study is p28, a cancer cell killing peptide. A peptide is a compound
made of amino acids, which are substances that the body uses to make protein. The p28
peptide was created from a protein called azurin. Azurin is created by a common
disease-causing bacteria named Pseudomonas Aeruginosa. p28 is experimental and has not yet
been tested in humans and has not been approved by the FDA for use in cancer subjects.
Up to 30 subjects may be enrolled in order to find 15 subjects who qualify for the study.
Subjects will be enrolled in groups of three, each starting at one of five progressively
higher dosage groups. The first group of three subjects will receive the lowest dose of p28
three times a week injected into a vein for four weeks. They will then be monitored for two
weeks. If no bad side effects are recorded, the initial three subjects will then receive
the second (higher) dose level of p28 three times a week for another four weeks, followed,
again, by two weeks of follow up. Additionally, three new subjects will be added to the
study and receive p28 on the same schedule, although this second group will start with the
second dose level. In this manner, 3 new subjects will be added every six weeks and start
treatment at the dose level to which previously enrolled groups have now progressed.
Subjects will be monitored weekly during their first six weeks and then every two weeks for
the remainder of the study. Monitoring will include physical exams, blood tests, EKG, and
appropriate radiographic imaging (CT, MRI, PET scan, and/or chest X-ray).
The entire study should take 32 weeks for subjects starting at dose 1, 26 weeks for subjects
starting at dose 2, 20 weeks for subjects starting at dose 3, 14 weeks for subjects starting
at dose 4, and 8 weeks for subjects starting at dose 5 (there is an additional 2 week
follow-up period at the end of the study for all subjects included in these figures). All
surviving subjects however, will be followed according to the normal follow-up schedule for
such subjects at the UIC Oncology Center.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical and laboratory adverse reactions will be closely monitored by periodic physical and laboratory examination.
Outcome Time Frame:
32 weeks
Safety Issue:
Yes
Principal Investigator
Michael A Warso, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Illinois Department of Surgical Oncology
Authority:
United States: Food and Drug Administration
Study ID:
CDGTI-p28-001
NCT ID:
NCT00914914
Start Date:
April 2009
Completion Date:
June 2011
Related Keywords:
- Refractory Solid Tumors
- Neoplasms
Name | Location |
|---|---|
| University of Illinois at Chicago Department of Surgical Oncology | Chicago, Illinois 60612 |
