Pre-surgical Androgen Deprivation Therapy With or Without Axitinib in Previously Untreated Prostate Cancer Patients With Known or Suspected LymphNode Metastasis
18 Years
N/A
Male
Prostate Cancer
Trial Information
Pre-surgical Androgen Deprivation Therapy With or Without Axitinib in Previously Untreated Prostate Cancer Patients With Known or Suspected LymphNode Metastasis
Study Drug:
Axitinib is designed to block the formation of new blood vessels, which are involved in the
growth and development of tumors.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the roll of the dice) to 1 of 2 groups:
- If you are in Group A, you will receive axitinib and hormonal therapy.
- If you are in Group B, you will receive hormonal therapy alone.
You will have a 2 out of 3 chance of being placed in Group A. You have a 1 out of 3 chance
of being placed in Group B.
Study Drug Administration:
All participants will receive hormonal therapy. The hormonal drug you receive will be
standard of care hormone therapy. The study doctor will decide what hormone therapy you will
receive and will explain when and how you should take the hormone therapy and any risks.
You will have 8 weeks of hormone therapy before you are assigned to a study group. After you
are assigned to a study group, you will receive up to 6 more months of hormone therapy.
If you are in Group A, you will also take 1 capsule of axitinib by mouth 2 times a day. You
will be asked to take your blood pressure 2 times a week and record it in a diary before
taking your axitinib dose. Note: If your blood pressure is above 150 systolic (the upper
number) OR above 100 diastolic (the lower number) or if you develop any symptoms related to
increased blood pressure please contact your study doctor immediately. You can take your
blood pressure at home or elsewhere, such as at the drug store or doctors office. Doses
should be taken about 12 hours apart and at about the same time each day, with food. If you
miss a dose, you may take it up to 3 hours late before the next scheduled dose; otherwise do
not make up the missed dose. Instead, skip the missed dose and take your next dose as
scheduled. If you vomit any time after taking a dose do not make it up, but instead take
your next dose as scheduled. You will be asked to keep a diary to help you keep track of
when you take each dose of the study drug. Record any missed or vomited doses in the diary.
Bring the diary with you to each visit.
Each cycle is 30 days. You should return all unused study drug and/or empty pill bottles at
the end of each cycle.
Study Visits:
At every visit, you will be asked about any side effects you have had and any drugs you may
be taking.
About 8 weeks after you begin hormonal therapy:
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 3-4 teaspoons) will be drawn for routine tests and to check your PSA. Your
blood will also be tested for levels of certain proteins.
- You will have an ultrasound-guided biopsy of the prostate with 10-12 samples collected.
You will be separately consented for this biopsy, which will describe the procedure
and its risks in more detail.
- Blood (about 2 tablespoons) will be drawn for routine tests. Your blood will also be
tested to check your thyroid function (Group A only).
- Urine will be collected for routine tests (Group A only).
- You will have an ECG (Group A only).
On Day 15 of Cycle 1 (Group A only):
- Your vital signs and weight will be measured.
- Blood (about 3-4 teaspoons) will be drawn for routine tests and to check your thyroid
function.
On Day 1 of Cycles 2, 3, and 5 (Group A only):
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 3-4 teaspoons) will be drawn for routine tests to check your PSA and
testosterone levels, and to check your thyroid function (Day 1 of Cycle 3 only).
- Urine will be collected for routine tests
About 3 months before surgery (Group B only):
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn to check your PSA and testosterone levels.
About 2 weeks before surgery or if you go off study early:
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- You will have a digital rectal exam.
- Your performance status will be recorded.
- Blood (about 3-4 teaspoons) will be drawn for routine tests and to check your PSA and
testosterone levels. Your blood will also be tested for levels of certain proteins.
- You will have a CT scan or MRI scan of the chest, abdomen, and pelvis to check the
status of the disease.
- You will have a bone scan to check the status of the disease.
- Blood (about 2 tablespoons) will be drawn for routine tests. Your blood will also be
tested to check your thyroid function (Group A only).
Length of Study:
You may receive the study drug(s) for about 8 months. You will be taken off study early if
the disease gets worse, if you have intolerable side effects, or if your study doctor thinks
it is in your best interest to stop.
Your participation on the study will be over once you have completed the follow-up visits
after surgery.
Surgery:
After 8 months of study treatment, you will have surgery to remove your prostate. You will
be asked to sign a separate consent form for this surgery, and the risks will be discussed
with you.
Long-Term Follow-Up:
At 1 month after your surgery:
- You will be asked about any drugs or treatments you may be receiving (including
over-the-counter drugs, herbal remedies, vitamins, and/or supplements).
- You will be asked about any side effects you have had.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for PSA and testosterone levels.
- If you are in Group A, blood (about 2 tablespoons) will be drawn for routine tests.
At 3 months after your surgery:
- Your medical history will be recorded.
- You will be asked about any disease-related symptoms and/or side effects you may have
had.
- You will have a physical exam, including measurement of your weight, height, and vital
signs.
- Your performance status will be recorded.
- Blood (about 3-4 teaspoons) will be drawn for routine tests and to check your PSA and
testosterone levels.
You will have follow-up visits every 3 months for the first year, every 4 months for the
second year, every 6 months in the third to fifth year, and 1 time a year after that unless
the disease worsens, you start taking hormone therapy, or you begin radiation treatments. At
these visits, blood (about 1 teaspoon) will be drawn to test your PSA level.
This is an investigational study. Axitinib is not FDA approved or commercially available.
Axitinib is currently being used for research purposes only.
Up to 54 patients will be enrolled in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Patients with adenocarcinoma of the prostate that in the opinion of the urologist
could be resected after response to systemic therapy. Ductal adenocarcinoma is
permitted.
2. Patients must be regarded as acceptable surgical risk for radical prostatectomy and
confirm their intention to undergo radical prostatectomy at the end of the
pre-surgical therapy.
3. ECOG performance status 2 or better.
4. All patients must have thorough tumor staging and meet at least one of the following
criteria: a. Either lymph node biopsy or lymph node dissection demonstrating lymph
node metastasis by prostate cancer; b. Non-bulky (< 5 cm) regional pelvic or distant
lymphadenopathy visualized on CT/MRI scan. Lymph node biopsy is required if < 2.0 cm
or in atypical distribution. c. Primary tumor Gleason score >/= 8 and serum PSA
concentration >/=25 ng/mL, indicating high risk of occult lymph node metastases. d.
Primary clinical tumor stage of T3 and Gleason score >/= 7, indicating high risk of
occult lymph node metastases. e. Primary tumor stage T4, indicating high risk of
occult lymph node metastases. Patients in any of these groups and less than 3 sites
of non-predominantly lytic bone metastasis will be still considered eligible for the
trial. The 2010 AJCC staging system will be followed.
5. Prior hormonal therapy (LHRH agonist/antagonist with or without antiandrogen) up to 8
weeks is permitted.
6. Patients must have adequate bone marrow function defined as an absolute peripheral
neutrophil count (ANC) of >/= 1,500/mm^3 and platelet count of >/= 100,000/mm^3;
adequate hepatic function defined with a total bilirubin of normal (ULN), and AST/ALT creatinine /= 60 mL/min (measured or calculated); and
urinary protein <2+ by urine dipstick (if >/= 2+, a 24-hour urine protein must show
protein < 2 g per 24 hours).
7. Patients or their partners must be surgically sterile or must agree to use effective
contraception while receiving study treatment and for at least 3 months thereafter.
The definition of effective contraception should be in agreement with local
regulation and based on the judgment of the principal investigator or a designated
associate.
8. Patients must 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, and willing and able to comply with scheduled visits, treatment
plans, laboratory tests, and other study procedures.
9. All patients must have a surgical and medical oncology consult prior to signing
informed consent.
Exclusion Criteria:
1. Patients with biopsy-proven small cell or sarcomatoid histology.
2. Patients with clinical or radiological evidence of bone (>/= 3 sites, or
predominantly lytic if < 3) or other extranodal metastasis.
3. Patients who have had prior chemotherapy, experimental agents for prostate cancer, or
patients receiving more than 8 weeks of prior hormone therapy will be excluded.
4. Gastrointestinal abnormalities such as inability to take oral medication; requirement
for intravenous alimentation; prior surgical procedures affecting absorption
including total gastric resection; treatment for active peptic ulcer disease in the
past 6 months; active gastrointestinal bleeding as evidenced by hematemesis,
hematochezia or melena in the past 3 months without evidence of resolution documented
by endoscopy or colonoscopy; malabsorption syndromes.
5. Anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors
(i.e., verapamil, ketoconazole, miconazole, itraconazole, erythromycin,
telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir,
lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine). Grapefruit juice
is also a CYP3A4 inhibitor.
6. Anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers
(i.e. carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin,
amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
7. Patients with any infectious process that, in the opinion of the investigator, could
worsen or its outcome be affected as a result of the investigational therapy.
8. Patients with symptomatic congestive heart failure, unstable angina or myocardial
infarction, coronary/peripheral artery bypass graft or repair, cerebrovascular
accident or transient ischemic attack in the 12 months prior to randomization; or
deep vein thrombosis or pulmonary embolism in the 6 months prior to randomization.
9. Persistently uncontrolled diabetes mellitus, oxygen-dependent lung disease, chronic
liver disease, or HIV infection.
10. Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg
and/or diastolic blood pressure >90 mmHg) despite antihypertensive medication, or
prior history of hypertensive crisis or hypertensive encephalopathy.
11. Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation).
12. Anticipation of need for major surgical procedure during the course of the study
other than as outlined by the protocol.
13. History of abdominal fistula or gastrointestinal perforation within 6 months prior to
randomization.
14. Serious, non-healing wound, active ulcer, or untreated bone fracture; any bone
fractures must be healed.
15. Known hypersensitivity to any component of axitinib or prior use of axitinib.
16. Second malignancies (excluding non-melanoma skin cancer) unless treated with curative
intent and disease-free for 3 years.
17. Overt psychosis, mental disability, otherwise incompetent to give informed consent,
or history of non-compliance.
18. Planned participation in any other experimental drug study.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Participants Progression-free 12 months after surgery
Outcome Description:
Time to Prostate-specific antigen (PSA)-progression measured from the date of radical prostatectomy to the occurrence of a serum PSA >1.0 ng/mL (confirmed by a second measurement at least 2 weeks apart). PSA-monitoring every 3 months after surgery for the first 12 months, every 4 months in the second year, every 6 months in the third to fifth year, and yearly thereafter until PSA or radiologic progression.
Outcome Time Frame:
12 months after surgery
Safety Issue:
No
Principal Investigator
Amado Zurita, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2011-0231
NCT ID:
NCT01409200
Start Date:
March 2012
Completion Date:
Related Keywords:
- Prostate Cancer
- Prostate cancer
- Adenocarcinoma of the prostate
- Ductal adenocarcinoma
- Androgen deprivation therapy
- ADT
- Hormonal therapy
- Suspected lymph node metastasis
- TxN1M0 or TxNxM1a
- Progression-free
- Pathologic complete response
- pCR
- Systemic therapy
- Radical prostatectomy
- Pelvic lymph node dissection
- Axitinib
- AG-013736
- Prostatic Neoplasms
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
