Cabazitaxel and Radiation For Patients With Pathologically Determined Stage 3 Prostate Cancer and/or Patients With PSA Elevation (>0.1- < 2.0 ng/mL)

• ClinicalTrials.gov Identifier: NCT01650285
• Recruitment Status: Terminated
• First Posted: July 26, 2012
• Results First Posted: June 29, 2015
• Last Update Posted: July 17, 2018
• Sponsor: Brown University
• Information provided by (Responsible Party): Dr Anthony Mega, Brown University

Study Description

Brief Summary:

There is a high relapse rate for patients who have undergone prostatectomy and have pathologic extracapsular prostate extension, positive surgical margins or seminal vesicle involvement (pathologic stage 3 disease). While adjuvant radiation improves progression-free and overall survival, approximately half of these patients will develop recurrence. Similarly, radiation therapy has become the standard salvage therapy for patients with rising PSA >0.1 - < 2.0 ng/mL. In common solid tumors such as NSCLC, head and neck cancer and upper gastrointestinal cancers, the addition of chemotherapy to radiation improves survival. It is hypothesized that the addition of radiosensitizing chemotherapy to standard adjuvant radiation will improve survival in patients with stage 3 prostate cancer after prostatectomy and patients with rising PSA < 2.0 ng.mL without detectable disease. Taxanes are powerful radiation enhancers since they synchronize tumor cells in G2/M the most radiosensitive phase of the cell cycle.17,18 Cabazitaxel is the most active taxane in the treatment of prostate cancer. Therefore, we propose a phase I study establishing the optimal dose of cabazitaxel with adjuvant radiation for stage 3 prostate cancer after prostatectomy (PSA undetectable - < 2.0 ng/mL). and for patients with persistent or rising PSA post prostatectomy (PSA >0.1 - < 2.0 ng/mL).

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Cabazitaxel	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cabazitaxel and Radiation For Patients With Pathologically Determined Stage 3 Prostate Cancer and/or Patients With PSA Elevation (>0.1- < 2.0 ng/mL) Following Radical Prostatectomy
• Study Start Date: January 2013
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: July 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cabazitaxel and radiation; Radiation therapy (RT) will be delivered to 64.8 Gy, using IMRT treatment Cabazitaxel will be administered IV every 21 days for 3 doses at the assigned dose level.	Drug: Cabazitaxel; Dose Level Day 1, 22, 43; 5.0 mg/m2; 10.0 mg/m2; 15.0 mg/m2; 20.0 mg/m2

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose of Cabazitaxel With Concurrent Adjuvant Radiation [ Time Frame: 2 mos ]
   The MTD was not determined secondary to the study closing early. That being said the numbers provided below show that 4 patients were treated on study to aide in the investigation of the MTD. Only 1 dose was fully evaluated which was 5mg/m2

Secondary Outcome Measures :

1. Number of Participants Experiencing a Toxicity Associated With Cabazitaxel and Adjuvant Radiation Following Prostatectomy for Patients With Stage 3 Prostate Cancer and for Patients With a PSA Elevation Post-Prostatectomy. [ Time Frame: During study treatment (approximately 8 weeks) through 30 days post treatment, approximately 12 weeks. ]
   Assess toxicity using CTCAE version 4.0. Number of patients who experienced a toxicity on the study. Not all toxicities are related to study treatment. Of note, there were no serious adverse events on this trial.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Conditions for Patient Eligibility

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

• Radical prostatectomy for adenocarcinoma of the prostate with at least one of the following:

  • Extracapsular tumor extension,
  • Positive surgical margins,
  • Seminal vesicle invasion
  • Regional lymph node positive (N1)
  • Post-prostatectomy PSA of > 0.1 - < 2.0 ng/mL at least 6 weeks after prostatectomy and within 30 days of registration in a patient with T2 or T3 disease at prostatectomy.
• No distant metastases.
• No prior pelvic or prostate radiation or chemotherapy for prostate cancer.
• ECOG performance status 0-1.
• Age>18.
• Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥ 1500 cells/mm3; platelet count ≥100,000 cells/mm3, Creatinine ≤ 1.5X upper limit of normal (if creatinine clearance 1.0-1.5x ULN, creatinine clearance will be calculated according to Chronic Kidney Disease Epidemiology Group formula and patients with creatinine clearance < 60 ml/min should be excluded),19 .Hgb > 9.0 g/dl, total bilirubin ≤ 1x ULN, and AST or ALT ≤ 2.5 x ULN.
• Life expectancy of at least 1 year.
• Must not have uncontrolled severe, intercurrent illness.
• No concurrent anticancer therapy.
• Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Signed study-specific consent form prior to study entry.
• Conditions for Patient Ineligibility

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Evidence of distant metastases (M1). Equivocal bone scans are allowed if plain films are negative for metastasis.
• Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (For example, carcinoma in situ of the oral cavity or bladder are permissible).
• History of severe hypersensitivity (> grade 3) reaction to Cabazitaxel or other drugs formulated with polysorbate 80.
• History of severe hypersensitivity (> grade 3) to docetaxel.
• Any uncontrolled severe, intercurrent illness (including uncontrolled diabetes)
• At least 4 weeks since any major surgery.
• Patients on concurrent anticancer therapy.
• PSA > 2ng/ml
• Concurrent or planned treatment with strong inhibitors or inducers of cytochrome p450 3A4/5 (a one-week wash out period is necessary for patients who are already on these treatments (see appendix H and I)
• Androgen deprivation therapy started prior to prostatectomy for > 6 months duration;
• Neoadjuvant chemotherapy prior to prostatectomy;
• Prior cryosurgery or brachytherapy of the prostate; prostatectomy should be the primary treatment and not a salvage procedure;
• Prior pelvic radiotherapy;

Contacts and Locations

Locations

United States, Rhode Island

Miriam Hospital

Providence, Rhode Island, United States, 06902

Sponsors and Collaborators

Brown University

Investigators

• Study Chair: Howard Safran, MD; Brown University
• Principal Investigator: anthony mega, md; Lifespan

More Information

• Responsible Party: Dr Anthony Mega, Priniciple Investigator, Brown University
• ClinicalTrials.gov Identifier: NCT01650285
• Other Study ID Numbers: BrUOG 246
• First Posted: July 26, 2012
• Results First Posted: June 29, 2015
• Last Update Posted: July 17, 2018
• Last Verified: June 2018

Keywords provided by Dr Anthony Mega, Brown University:

Prostate Cancer; Radical prostatectomy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases