Antiandrogen Therapy With or Without Axitinib Before Surgery in Treating Patients With Previously Untreated Prostate Cancer With Known or Suspected Lymph Node Metastasis
Primary Purpose
Metastatic Malignant Neoplasm in Lymph Node, Prostate Ductal Adenocarcinoma, Stage III Prostate Adenocarcinoma AJCC v7
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Antiandrogen Therapy
Axitinib
Radical Prostatectomy
Regional Lymph Node Dissection
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Malignant Neoplasm in Lymph Node
Eligibility Criteria
Inclusion Criteria:
- 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
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status 2 or better
All patients must have thorough tumor staging and meet at least one of the following criteria:
- Either lymph node biopsy or lymph node dissection demonstrating lymph node metastasis by prostate cancer
- Non-bulky (< 5 cm) regional pelvic or distant lymphadenopathy visualized on computed tomography (CT)/magnetic resonance imaging (MRI) scan; lymph node biopsy is required if < 2.0 cm or in atypical distribution
- Primary tumor Gleason score >= 8 and serum prostate-specific antigen (PSA) concentration >= 25 ng/mL, indicating high risk of occult lymph node metastases
- Primary clinical tumor stage of T3 and Gleason score >= 7, indicating high risk of occult lymph node metastases
- 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 American Joint Committee on Cancer (AJCC) staging system will be followed
- Prior hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist with or without antiandrogen) up to 8 weeks is permitted
- Absolute peripheral neutrophil count (ANC) of >= 1,500/mm^3
- Platelet count of >= 100,000/mm^3
- Total bilirubin of =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
- Serum creatinine =< 1.5 x ULN or clearance >= 60 mL/min (measured or calculated)
- Urinary protein < 2+ by urine dipstick (if >= 2+, a 24-hour urine protein must show protein < 2 g per 24 hours)
- 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
- Patients must sign the current institutional review board (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
- All patients must have a surgical and medical oncology consult prior to signing informed consent
Exclusion Criteria:
- Patients with biopsy-proven small cell or sarcomatoid histology
- Patients with clinical or radiological evidence of bone (>= 3 sites, or predominantly lytic if < 3) or other extranodal metastasis
- 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
- 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
- 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
- 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)
- 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
- 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
- Persistently uncontrolled diabetes mellitus, oxygen-dependent lung disease, chronic liver disease, or human immunodeficiency virus (HIV) infection
- 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
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Anticipation of need for major surgical procedure during the course of the study other than as outlined by the protocol
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization
- Serious, non-healing wound, active ulcer, or untreated bone fracture; any bone fractures must be healed
- Known hypersensitivity to any component of axitinib or prior use of axitinib
- Second malignancies (excluding non-melanoma skin cancer) unless treated with curative intent and disease-free for 3 years
- Overt psychosis, mental disability, otherwise incompetent to give informed consent, or history of non-compliance
- Planned participation in any other experimental drug study
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm I (antiandrogen therapy, axitinib, surgery)
Arm II (antiandrogen therapy, surgery)
Arm Description
Patients receive antiandrogen therapy per standard care and axitinib PO BID for 4 months. Patients then undergo radical prostatectomy and pelvic lymph node dissection.
Patients receive antiandrogen therapy per standard care for 4 months and then undergo radical prostatectomy and pelvic lymph node dissection.
Outcomes
Primary Outcome Measures
Participants Progression-free 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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01409200
First Posted
August 2, 2011
Last Updated
October 2, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01409200
Brief Title
Antiandrogen Therapy With or Without Axitinib Before Surgery in Treating Patients With Previously Untreated Prostate Cancer With Known or Suspected Lymph Node Metastasis
Official Title
Pre-Surgical Androgen Deprivation Therapy With or Without Axitinib in Previously Untreated Prostate Cancer Patients With Known or Suspected Lymph Node Metastasis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 26, 2012 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This randomized phase IIA trial studies how well antiandrogen therapy works with or without axitinib before surgery in treating patients with previously untreated prostate cancer that is known or suspected to have spread to lymph nodes. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as antiandrogen therapy may lessen the amount of androgen made by the body. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if antiandrogen therapy is more effective with or without axitinib before surgery in treating patients with prostate cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To compare the proportion of patients progression-free one year after treatment with axitinib plus androgen deprivation versus (vs.) androgen deprivation therapy alone and surgery in newly diagnosed prostate cancer patients with lymph node metastases (TxN1M0 or TxNxM1a) or clinical suspicion of lymph node metastases.
SECONDARY OBJECTIVES:
I. To compare the rate of pathologic complete response (pCR) in the primary tumor.
II. To evaluate time to progression. III. Describe the perioperative and postoperative morbidity of pre-surgical treatment.
IV. Evaluate the effects of a 6-month time course of androgen deprivation with or without axitinib in prostate cancer tissue and blood.
V. Develop a prospective tissue archive of prostate tumors that have metastasized to lymph nodes.
OUTLINE:
Patients receive antiandrogen therapy per standard care for 8 weeks.
Patients are then randomized to 1 of 2 treatment arms.
ARM I: Patients receive antiandrogen therapy per standard care and axitinib orally (PO) twice daily (BID) for 4 months. Patients then undergo radical prostatectomy and pelvic lymph node dissection.
ARM II: Patients receive antiandrogen therapy per standard care for 4 months and then undergo radical prostatectomy and pelvic lymph node dissection.
After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Malignant Neoplasm in Lymph Node, Prostate Ductal Adenocarcinoma, Stage III Prostate Adenocarcinoma AJCC v7, Stage IV Prostate Adenocarcinoma AJCC v7
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
73 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (antiandrogen therapy, axitinib, surgery)
Arm Type
Experimental
Arm Description
Patients receive antiandrogen therapy per standard care and axitinib PO BID for 4 months. Patients then undergo radical prostatectomy and pelvic lymph node dissection.
Arm Title
Arm II (antiandrogen therapy, surgery)
Arm Type
Active Comparator
Arm Description
Patients receive antiandrogen therapy per standard care for 4 months and then undergo radical prostatectomy and pelvic lymph node dissection.
Intervention Type
Drug
Intervention Name(s)
Antiandrogen Therapy
Other Intervention Name(s)
ADT, Androgen Deprivation Therapy, Anti-androgen Therapy, Anti-androgen Treatment, Antiandrogen Treatment, Hormone Deprivation Therapy, Hormone-Deprivation Therapy
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Axitinib
Other Intervention Name(s)
AG-013736, AG013736, Inlyta
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Radical Prostatectomy
Other Intervention Name(s)
Prostatovesiculectomy
Intervention Description
Undergo radical prostatectomy
Intervention Type
Procedure
Intervention Name(s)
Regional Lymph Node Dissection
Intervention Description
Undergo pelvic lymph node dissection
Primary Outcome Measure Information:
Title
Participants Progression-free 12 months after surgery
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.
Time Frame
12 months after surgery
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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
Eastern Cooperative Oncology Group (ECOG) performance status 2 or better
All patients must have thorough tumor staging and meet at least one of the following criteria:
Either lymph node biopsy or lymph node dissection demonstrating lymph node metastasis by prostate cancer
Non-bulky (< 5 cm) regional pelvic or distant lymphadenopathy visualized on computed tomography (CT)/magnetic resonance imaging (MRI) scan; lymph node biopsy is required if < 2.0 cm or in atypical distribution
Primary tumor Gleason score >= 8 and serum prostate-specific antigen (PSA) concentration >= 25 ng/mL, indicating high risk of occult lymph node metastases
Primary clinical tumor stage of T3 and Gleason score >= 7, indicating high risk of occult lymph node metastases
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 American Joint Committee on Cancer (AJCC) staging system will be followed
Prior hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist with or without antiandrogen) up to 8 weeks is permitted
Absolute peripheral neutrophil count (ANC) of >= 1,500/mm^3
Platelet count of >= 100,000/mm^3
Total bilirubin of =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
Serum creatinine =< 1.5 x ULN or clearance >= 60 mL/min (measured or calculated)
Urinary protein < 2+ by urine dipstick (if >= 2+, a 24-hour urine protein must show protein < 2 g per 24 hours)
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
Patients must sign the current institutional review board (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
All patients must have a surgical and medical oncology consult prior to signing informed consent
Exclusion Criteria:
Patients with biopsy-proven small cell or sarcomatoid histology
Patients with clinical or radiological evidence of bone (>= 3 sites, or predominantly lytic if < 3) or other extranodal metastasis
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
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
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
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)
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
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
Persistently uncontrolled diabetes mellitus, oxygen-dependent lung disease, chronic liver disease, or human immunodeficiency virus (HIV) infection
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
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Anticipation of need for major surgical procedure during the course of the study other than as outlined by the protocol
History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization
Serious, non-healing wound, active ulcer, or untreated bone fracture; any bone fractures must be healed
Known hypersensitivity to any component of axitinib or prior use of axitinib
Second malignancies (excluding non-melanoma skin cancer) unless treated with curative intent and disease-free for 3 years
Overt psychosis, mental disability, otherwise incompetent to give informed consent, or history of non-compliance
Planned participation in any other experimental drug study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amado J Zurita Saavedra
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center
Learn more about this trial
Antiandrogen Therapy With or Without Axitinib Before Surgery in Treating Patients With Previously Untreated Prostate Cancer With Known or Suspected Lymph Node Metastasis
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