Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA

Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA Failure With Biopsy Proven Local Recurrence After Initial Definitive Radiotherapy

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01531205

Enrollment

Registered

2012-02-10

Start date

2012-05-31

Completion date

2013-10-31

Last updated

2014-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Keywords

recurrent, high risk

Brief summary

The aim of this study is to test whether adding chemotherapy/cabazitaxel and hormonal/androgen deprivation therapy before surgical removal of your prostate would improve the outcome of salvage surgery for locally recurrent prostate cancer after the initial primary radiation therapy.

Detailed description

In this study, all participants will receive cabazitaxel chemotherapy, which is approved as a second line chemotherapy for treating metastatic prostate cancer. Standard hormone or androgen ablation therapy will also be used as part of the chemohormonal therapy prior to the surgery.

Interventions

DRUGAndrogen Ablation

All patients will receive luteinizing hormone-releasing hormone (LHRH) agonist therapy (leuprolide or goserelin acetate) concurrent with Cabazitaxel, before surgery. A course of bicalutamide 50 mg daily orally for 14-21 days is recommended for patients starting LHRH agonist therapy and suspected to be at risk for tumor flare, e.g., significant obstructive urinary symptoms and will be optional in other patients.

DRUGCabazitaxel

Intravenous treatment with Cabazitaxel 25 mg/m\^2 is given on day 1 every 21 days. A cycle of chemotherapy will be defined as 21 days. A total of four cycles of combination therapy are planned for a total duration of 12 weeks (before surgery), starting within 3 weeks of protocol entry, to be given concurrent with hormone therapy.

DRUGSalvage Therapy

Patients will undergo 4 cycles of chemotherapy in conjunction with LHRH agonist therapy (before surgery) subsequent to which they will have their serum Prostate-specific antigen (PSA), bone scan, abdominal pelvic computed tomography (CT) or magnetic resonance imaging (MRI) repeated. Patients with a detectable metastatic diseases will be removed from the study. Salvage surgery will be performed within 8 weeks after the completion of Cabazitaxel chemotherapy. For patients who achieved undetectable PSA following surgery, androgen deprivation therapy will be discontinued.

DRUGNeoadjuvant Treatment - Hormonal Therapy

All treatment will be given on an outpatient basis. Treatment should start within 3 weeks of protocol entry. All patients will receive androgen ablation with LHRH agonist therapy in conjunction with the 4 cycles of Cabazitaxel for neoadjuvant chemohormonal therapy. Androgen ablative therapy will be discontinued before surgery. A course of bicalutamide 50 mg daily orally for 14-21 days is recommended for patients starting LHRH agonist therapy and suspected to be at risk for tumor flare, e.g., significant obstructive urinary symptoms and will be optional in other patients.

DRUGNeoadjuvant Treatment - Cabazitaxel

All treatment will be given on an outpatient basis and should start within 3 weeks of protocol entry. Intravenous treatment with Cabazitaxel is given on Day 1 every 3 weeks. A cycle of combination therapy will be defined as 3 weeks. A total of 4 cycles of combination therapy are planned before surgery for a total duration of 12 weeks. Cabazitaxel will be administered before surgery by one-hourly infusions via central or peripheral intravenous access at a dose of 25 mg/m\^2 as a one hour intravenous infusion in combination with oral prednisone 10 mg administered daily throughout Cabazitaxel treatment. It is advised that all patients receiving Cabazitaxel have a reliable form of venous access, e.g., central venous catheter to ensure their ability to receive therapy without undue delay.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy must be more than 10 years * Peripheral neuropathy: must be \</= grade 1 * A minimum PSA of 1 ng/ml if not on androgen deprivation therapy * Patients must have one of the following criteria to be eligible: * PSA recurrence with a doubling time of less than 9 months (calculated by at least 3 PSA values that were obtained at least 4 weeks apart) * Prostatic biopsy Gleason Grade of \>/= 8 at the time of initial biopsy prior to radiation therapy and as determined by either an outside pathology report or on review of slides by our institutional pathologist(s) * Clinical stage of \>/= T3 (defined as evidence of extracapsular or seminal vesicle extension on digital rectal examination or transrectal ultrasonography) either at the time of initial diagnosis or following radiotherapy * Prior radiation therapy of any type including external beam radiotherapy, brachytherapy, high dose radiotherapy, or proton therapy * Positive prostate biopsy documenting local recurrence following radiation therapy * Prior androgen deprivation therapy up to a total duration of 36 months is allowable. * Patients who are on LHRH analog therapy should continue such therapy provided that the patient does not have castration resistant prostate cancer (rising PSA in the presence of castrate levels of serum testosterone, ie \< 50 ng/dl). Androgen deprivation therapy other than LHRH analog should be discontinued 4 weeks prior to study enrollment. * All prostatic carcinoma variants except small cell carcinoma of the prostate will be allowed. * Patients must have no evidence of metastatic diseases on the bone scan and an abdominal/pelvic CT or MRI performed within 30 days of study enrollment. * All patients must be regarded as acceptable anesthetic risk for salvage surgery (salvage radical prostatectomy, salvage cystoprostatectomy, salvage total pelvic exenteration) and confirm their intention to undergo salvage surgery at the end of the neoadjuvant chemohormonal therapy. * Patients must have adequate bone marrow function defined as an absolute peripheral granulocyte count of \> 1,500/mm\^3 and platelet count of \> 100,000/mm\^3; adequate hepatic function defined with a total bilirubin of \< 1.5 mg/dl and aspartic transaminase/alanine transaminase (AST/ALT) \< 1.5 X the upper limits of normal (ULN); adequate renal function defined as serum creatinine clearance \> 60 ml/min (measured or calculated). * Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * Patients must sign an informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution. * All patients must be evaluated in the Department of Genitourinary Oncology prior to signing informed consent.

Exclusion criteria

* Patients with small cell histology * Patients with clinical, radiological, or pathological evidence of bone, lymph node or visceral metastasis (liver or lung metastasis) * Castration resistant prostate cancer defined as rising PSA profile in setting of castrate levels of testosterone (serum testosterone \< 50 ng/dl) * Prior chemotherapy * Patients with severe or uncontrolled intercurrent infection * Patients with New York Heart Association (NYHA) Class III/IV congestive heart failure, unstable angina or history of myocardial infarction within the last 6 months * Contraindications to corticosteroids * Uncontrolled severe hypertension, persistently uncontrolled diabetes mellitus, oxygen dependent lung disease, chronic liver disease or HIV infection * Second malignancies (excluding non-melanoma skin cancer) unless disease-free for 3 years * Overt psychosis, mental disability or otherwise incompetent to give informed consent * Patients with a history of severe hypersensitivity reaction to Cabazitaxel® or other drugs formulated with polysorbate 80

Design outcomes

Primary

Measure	Time frame	Description
Surgical Margin Negative Rate (SM Rate)	One Year	Post surgery percentage of participants with negative surgical margin. To determine the surgical margin negative rate in patients who have undergone chemohormonal therapy followed by surgery for biopsy proven androgen-dependent high risk locally recurrent prostate cancer following primary radiation therapy. Margin: The edge or border of the tissue removed in cancer surgery. The margin is described as negative or clean when the pathologist finds no cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. The margin is described as positive or involved when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed.

Secondary

Measure	Time frame	Description
Incidence of PSA Progression Free Survival (PFS)	Four Months	Percentage of participants with stable (has not increased) or undetectable PSA post surgery. To assess Prostate-specific antigen(PSA)-progression free survival and prostate cancer specific survival for patients treated by chemohormonal therapy followed by salvage surgery for biopsy proven androgen-dependent high-risk locally recurrent prostate cancer following radiation therapy.
Incidence of Complete Response (CR)	One Year	Percentage of participants with CR post surgery. To evaluate the pathological complete response rate to androgen ablation plus Cabazitaxel in patients with locally recurrent prostate cancer following radiation therapy. Pathological Complete Response (pCR): Participants with no residual cancer in the local resection specimen and pelvic lymph nodes will be considered pCR.
Incidence of Perioperative and Postoperative Morbidity	One Year	Number of events. To access the perioperative and postoperative morbidity with salvage surgery after neoadjuvant hormonal ablation and Cabazitaxel.
Incidence of Detecting Circulating Tumor Cells (CTC)	One Year	To determine the feasibility of detecting circulating tumor cells in this patient population. CTC results per patient in milliliters.

Countries

United States

Participant flow

Recruitment details

Participants were recruited at Moffitt Cancer Center from May 15, 2012 to September 27, 2013.

Participants by arm

Arm	Count
Experimental: Drug and Hormonal Therapy With Salvage Surgery Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up	2
Total	2

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Did not proceed to surgery	1

Baseline characteristics

Characteristic	Experimental: Drug and Hormonal Therapy With Salvage Surgery
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Age, Continuous	69 years
Region of Enrollment United States	2 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	2 / 2
serious Total, serious adverse events	0 / 2

Arm	Measure	Value (NUMBER)
Experimental: Drug and Hormonal Therapy With Salvage Surgery	Incidence of PSA Progression Free Survival (PFS)	0 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026