Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA

NCT01531205 | Terminated Phase 2 Results DMC

• 1 other identifier: MCC-16684
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

recurrent; high risk

Outcome Measures

Primary Outcomes (1)

• Surgical Margin Negative Rate (SM Rate)

  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.

  One Year

Secondary Outcomes (4)

• Incidence of PSA Progression Free Survival (PFS)

  Four Months

• Incidence of Complete Response (CR)

  One Year

• Incidence of Perioperative and Postoperative Morbidity

  One Year

• Incidence of Detecting Circulating Tumor Cells (CTC)

  One Year

Study Arms (1)

Drug and Hormonal Therapy with Salvage Surgery

EXPERIMENTAL

Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up

Drug: Androgen Ablation; Drug: Cabazitaxel; Drug: Salvage Therapy; Drug: Neoadjuvant Treatment - Hormonal Therapy; Drug: Neoadjuvant Treatment - Cabazitaxel

Interventions

Androgen Ablation DRUG

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.

Also known as: goserelin acetate (Zoladex®), leuprolide acetate (Lupron®), bicalutamide (Casodex®)

Drug and Hormonal Therapy with Salvage Surgery

Cabazitaxel DRUG

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.

Also known as: Jevtana®

Drug and Hormonal Therapy with Salvage Surgery

Salvage Therapy DRUG

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.

Also known as: prostatectomy

Drug and Hormonal Therapy with Salvage Surgery

Neoadjuvant Treatment - Hormonal Therapy DRUG

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.

Drug and Hormonal Therapy with Salvage Surgery

Neoadjuvant Treatment - Cabazitaxel DRUG

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.

Also known as: Jevtana®

Drug and Hormonal Therapy with Salvage Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Sanofi: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Recurrence

Interventions

Goserelin; Leuprolide; bicalutamide; cabazitaxel; Salvage Therapy; Prostatectomy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Therapeutics; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Limitations and Caveats

Study was closed early due to low accrual. Investigators had planned to follow 25 participants from On Study through End of Follow-up, up to 10 years.

Results Point of Contact

• Title: Julio Pow-Sang, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

julio.powsang@moffitt.org

813-745-2226

Study Officials

• Julio Pow-Sang, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2012
• First Posted: February 10, 2012
• Study Start: May 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 5, 2014
• Results First Posted: August 5, 2014

Record last verified: 2014-07

Locations

US (1)