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A First-in-Man, Phase I Evaluation of A Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Castrate-Resistant Prostate Cancer and No Standard Treatment Options


Phase 1
18 Years
N/A
Open (Enrolling)
Male
Prostate Cancer

Thank you

Trial Information

A First-in-Man, Phase I Evaluation of A Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Castrate-Resistant Prostate Cancer and No Standard Treatment Options


The Study Drug:

PROHIBITIN-TP01 is designed to destroy "white fat" (the type of fat that collects around the
stomach and is associated with obesity in men). Fat is known to produce substances that can
promote prostate cancer growth. Investigators want to learn if decreasing fat can slow the
growth of prostate cancer.

This is the first study using PROHIBITIN-TP01 in humans.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of PROHIBITIN-TP01 based on when you join this study. Up to 5 dose levels of
PROHIBITIN-TP01 will be tested. Three (3) participants will be enrolled at each dose
level. The first group of participants will receive the lowest dose level. Each new group
will receive a higher dose than the group before it, if no intolerable side effects were
seen. This will continue until the highest tolerable dose of PROHIBITIN-TP01 is found.

Study Drug Administration:

You will receive PROHIBITIN-TP01 as an injection under the skin 1 time each day for 28 days.

Study Visits:

On Days 1, 8, 15 and 22:

- You will have a physical exam, including measurement of your weight.

- Your performance status will be recorded.

- Blood (about 3 teaspoons) will be drawn for routine tests. You will be required to
fast for about 8 hours before this blood test.

- You will be asked about any symptoms or side effects you may have had since your last
visit and about any other drugs you may be taking.

- Blood (about 2 teaspoons) will be drawn for Pharmacokinetic (PK) testing 10 minutes, 30
minutes, 1 hour, and 4 hours after you receive the Day 1 and Day 22 dose of
PROHIBITIN-TP01.

- You will have an ECG either right before or within 4 hours after you receive the study
drug (Days 1, 15, and 22 only).

Length of Study Drug Administration:

You will receive the study drug for up to 28 days. You will no longer be able to receive
the study drug if the disease gets worse or intolerable side effects occur.

Follow-up Visit:

Within 7 days after you stop receiving the study drug, the following procedures will be
performed:

- You will have a physical exam, including measurement of your weight, as well as
measurements of your waist and hips.

- Your performance status will be recorded.

- Blood (about 3 teaspoons) will be drawn for routine tests. This testing will also
include a measurement of your prostate-specific antigen (PSA), testosterone,
cholesterol, and other research tests that may show how the study drug affected you.

- You will be asked about symptoms or any side effects you have had since your last
visit.

- You will have computer tomography (CT) or magnetic resonance imaging (MRI) scans and a
chest x-ray to check the status of the disease.

- You will have an ECG

Thirty (30) days after you stop receiving the study drug, the following procedures will be
performed:

- You will have a physical exam, including measurement of your weight.

- Your performance status will be recorded.

- Blood (about 3 teaspoons) will be drawn for routine tests.

- Blood (about 3 teaspoons - in addition to that listed above) will be collected to learn
if your immune system reacts to PROHIBITIN-TP01 by forming antibodies.

- You will be asked about symptoms or any side effects you have had since your last
visit.

- You will have an ECG

Long-Term Follow-Up:

You will be contacted by phone or e-mail every 3 months for 1 year and asked about your
kidney function, current weight, prostate cancer status, and any side effects you may have
had. Each phone call will last up to 5 minutes.

This is an investigational study. PROHIBITIN-TP01 is not FDA approved or commercially
available. It is currently being used for research purposes only.

Up to 39 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Have histologically confirmed carcinoma of the prostate, with clinically significant
castrate-resistant progression and a BMI defined as obese (i.e. > 30 kg/m^2). Any
histologic variant is acceptable aside from pure small cell carcinoma.

2. Have progression within the previous 3 months in the face of a serum testosterone of
less than 50 ng/dL, and have no standard options for therapy. In general, this means
having experienced disease progression (or intolerable side effects) in the context
of a second-line hormonal therapy (such as ketoconazole, abiraterone, low-dose
dexamethasone, anti-androgens, etc.) in addition to a docetaxel-based therapy, or two
cytotoxic therapies, at least one of which included a taxane. Patients are also
considered to be eligible if they decline to have additional cytotoxic therapy after
failure of a taxane-based regimen. Patients must be at least 3 weeks from their last
treatment prior to registration on this study (excluding ongoing therapy to suppress
testosterone, which must also be continued during this trial).

3. Have an ECOG performance status 0, 1 or 2

4. Have adequate bone marrow function defined as an absolute peripheral granulocyte
count of >/= 1,000/mm^3 and platelet count of >/= 100,000/mm^3; hemoglobin >/= 8.0
g/dL (without transfusion or growth factor support)

5. Have adequate hepatic function defined as a total bilirubin of
6. Have adequate renal function defined as serum creatinine normal or creatinine clearance >/= 60 mL/min (measured or calculated). In addition,
patients must have a 24 hr urine collection showing less than 2000 mg of protein.
EXCEPTION: Patients with hematuria will be eligible with up to 3000 mg protein per 24
hours provided they do not have casts, eosinophiluria or electrolyte wasting.

7. Have adequate cardiovascular function as defined by: i) a normal B-type Natruetic
Peptide (BNP) with ii) no signs or symptoms suggestive of cardiac disease and iii) a
normal ECG. If these criteria are not met, patients must have an echocardiogram or
multigated cardiac scan (MUGA) showing an EF of 45% or greater with no more than
"mild" diastolic dysfunction and a BNP of < 200 pg/mL to be eligible.

8. Sign the current IRB approved informed consent indicating that they are aware of the
investigational nature of this study, in keeping with the policies of the institution

Exclusion Criteria:

1. Small cell prostate cancer

2. Infectious process, which, in the opinion of the investigator, could worsen or its
outcome be affected, as a result of the investigational therapy

3. Any of the following in previous 6 months: NYHA Class III/IV congestive heart
failure, unstable angina, cerebrovascular accident (including transient ischemic
attack), pulmonary embolism or myocardial infarction (by ECG or serologic criteria)

4. Significant co-morbidity that could affect the safety or evaluability of
participants, specifically including: i) Chronically uncontrolled hypertension,
defined conventionally as consistent systolic pressures above 140 or diastolic
pressures above 90 despite therapy. Note that this may be better established with
home BP readings than with clinic visit results. Note further that this is NOT a
criterion related to particular BP results at the time of assessment for eligibility,
nor does it apply to acute BP excursions that are related to iatrogenic causes, acute
pain or other transient, reversible causes. The intent is to exclude patients that
may have unrecognized renal damage from chronic, uncontrolled hypertension, NOT to
exclude patients who may be hypertensive acutely. There are no absolute criteria for
BP readings with respect to eligibility (as determined by treating physician).

5. ( # 9 cont'd) (ii) Uncontrolled diabetes mellitus, defined as: Hgb A1c >8.5%; or
symptomatic hypoglycemic episodes > 1 per week during the two months prior to
eligibility evaluation; or more than 1 glucose excursion to >300 mg/dL in prior two
months--unless clearly iatrogenic and the cause has been eliminated iii) Lung disease
requiring supplemental oxygen iv) Known chronic liver disease causing either fibrosis
or synthetic dysfunction v) Known HIV infection vi) Overt psychosis, mental
disability or being otherwise incompetent to grant informed consent or a history of
non-compliance with medical care.

6. Hydronephrosis (either bilateral or involving a solitary kidney) that has not been
addressed by means of a nephrostomy or indwelling stent. EXCEPTION: Non-obstructive
hydronephrosis in setting of prior urinary diversion is consistent with eligibility.

7. Patients require ongoing therapy with non-steroidal anti-inflammatory drugs (NSAIDs),
i.v. vancomycin, aminoglycosides, or other potently nephrotoxic drugs, and must agree
to abstain from NSAIDs from the time the consent is signed up until 30 days after the
last dose of study drug is received, other than low-dose aspirin (81 mg/day or less).

8. Any other medical condition that in the opinion of the principal investigator would
compromise the ability to deliver or evaluate study drug.

9. Unwillingness to maintain adequate contraception measures for the entire course of
the study

10. Age < 18 years.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Description:

Maximum Tolerated Dose (MTD) defined as that without dose-limiting toxicity 30 days after the last dose of study drug.

Outcome Time Frame:

28 day cycle

Safety Issue:

Yes

Principal Investigator

Lance Pagliaro, MD, BA

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0369

NCT ID:

NCT01262664

Start Date:

May 2012

Completion Date:

Related Keywords:

  • Prostate Cancer
  • Advanced prostate cancer
  • Castrate-Resistant Prostate Cancer
  • Prohibitin-TP01
  • Prostatic Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030