Neoadjuvant Axitinib in Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01409200
First received: August 2, 2011
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Other: ADT Therapy
Drug: Axitinib
Procedure: Prostatectomy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pre-surgical Androgen Deprivation Therapy With or Without Axitinib in Previously Untreated Prostate Cancer Patients With Known or Suspected LymphNode Metastasis

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Participants Progression-free 12 months after surgery [ Time Frame: 12 months after surgery ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 54
Study Start Date: March 2012
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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 + 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.
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.

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01409200

Contacts
Contact: Amado Zurita, MD 713-792-2830

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: Amado Zurita, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01409200     History of Changes
Other Study ID Numbers: 2011-0231, NCI-2011-02749
Study First Received: August 2, 2011
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Genital Diseases, Male
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Androgens
Axitinib
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014