Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA

Phase 2

Terminated

• Conditions: Prostate Cancer
• Interventions: Drug: Androgen Ablation; Drug: Cabazitaxel; Drug: Salvage Therapy; Drug: Neoadjuvant Treatment - Hormonal Therapy; Drug: Neoadjuvant Treatment - Cabazitaxel

• Registration Number: NCT01531205
• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

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.

Study Timeline

• Study First Submitted: 2012-02-08
• Study First Submitted QC: 2012-02-09
• Study First Posted: 2012-02-10
• Study Start: 2012-05
• Primary Completion: 2013-09
• Study Completion: 2013-10
• Status Verified: 2014-07
• Results First Submitted: 2014-07-08
• Results First Submitted QC: 2014-08-04
• Results First Posted: 2014-08-05
• Last Update Submitted: 2014-11-04
• Last Update Posted: 2014-11-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 2

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Drug and Hormonal Therapy with Salvage Surgery	Neoadjuvant Treatment - Hormonal Therapy	Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up
Drug and Hormonal Therapy with Salvage Surgery	Neoadjuvant Treatment - Cabazitaxel	Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up
Drug and Hormonal Therapy with Salvage Surgery	Salvage Therapy	Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up
Drug and Hormonal Therapy with Salvage Surgery	Androgen Ablation	Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up
Drug and Hormonal Therapy with Salvage Surgery	Cabazitaxel	Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 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 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.

Trial Locations

Locations (1)

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States