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Neoadjuvant Axitinib in Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01409200
Recruitment Status : Recruiting
First Posted : August 4, 2011
Last Update Posted : October 20, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

August 2, 2011
August 4, 2011
October 20, 2017
March 2012
March 2019   (Final data collection date for primary outcome measure)
Participants Progression-free 12 months after surgery [ Time Frame: 12 months after surgery ]
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.
Same as current
Complete list of historical versions of study NCT01409200 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Neoadjuvant Axitinib in Prostate Cancer
Pre-surgical Androgen Deprivation Therapy With or Without Axitinib in Previously Untreated Prostate Cancer Patients With Known or Suspected Lymph Node Metastasis

The goal of this clinical research study is learn if adding axitinib to hormonal therapy can help to control prostate cancer when given before surgery. The safety of this drug will also be studied.

This is an investigational study. Axitinib is FDA approved for kidney cancer. Axitinib is currently being used for research purposes only in prostate cancer.

Up to 72 patients will be enrolled in this study. All will be enrolled at MD Anderson.

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 4 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.

On Day 1 of Cycles 2 and 3 (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. Part of this blood will be used to check your thyroid function (Cycle 2 only).
  • Urine will be collected for routine tests

About 2 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 6 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 6 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 and to check your thyroid function.

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 3-4 teaspoons) will be drawn for routine tests and to check your PSA and testosterone levels.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Prostate Cancer
  • Other: ADT Therapy
    ADT for 8 weeks (specific drugs/dose/frequency not mandated by protocol) then up to 6 more months of hormone therapy following assignment to study group.
  • Drug: Axitinib
    5 mg by mouth twice a day for 30 day cycle.
    Other Name: AG-013736
  • Procedure: Prostatectomy
    Radical prostatectomy and pelvic lymph node dissection approximately 8 months after androgen deprivation therapy (ADT) with or without open label Axitinib.
  • Experimental: ADT Group
    Androgen deprivation therapy (ADT) for 8 weeks (specific drugs/dose/frequency not mandated by protocol) then up to 6 more months of hormone therapy following assignment to study group. Radical prostatectomy and pelvic lymph node dissection approximately 8 months after androgen deprivation therapy (ADT) with or without open label Axitinib.
    Interventions:
    • Other: ADT Therapy
    • Procedure: Prostatectomy
  • Experimental: ADT + Axitinib
    Androgen deprivation therapy (ADT) with Axitinib 5 mg orally twice/day for 30 days. Radical prostatectomy and pelvic lymph node dissection approximately 8 months after androgen deprivation therapy (ADT) with or without open label Axitinib.
    Interventions:
    • Other: ADT Therapy
    • Drug: Axitinib
    • Procedure: Prostatectomy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
March 2019
March 2019   (Final data collection date for primary outcome measure)

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. 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 </= 1.5 x upper limit of normal (ULN), and AST/ALT </= 2.5 x ULN; adequate renal function defined as serum creatinine </= 1.5 x ULN or clearance >/= 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.
Sexes Eligible for Study: Male
18 Years and older   (Adult, Senior)
No
Contact: Amado Zurita, MD 713-792-2830
United States
 
 
NCT01409200
2011-0231
NCI-2011-02749 ( Registry Identifier: NCI CTRP )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Pfizer
Principal Investigator: Amado Zurita, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP