Bicalutamide and RO4929097 in Treating Patients With Previously Treated Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01200810
First received: September 10, 2010
Last updated: May 3, 2013
Last verified: December 2012
  Purpose

This partially randomized phase II trial is studying how well giving bicalutamide together with RO4929097 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bicalutamide together with RO4929097 may be an effective treatment for prostate cancer


Condition Intervention Phase
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Other: placebo
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Drug: bicalutamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Peripheral Androgen Blockade With Bicalutamide Followed by Placebo or Treatment With the Gamma Secretase Inhibitor RO4929097 in Men With Rising PSA After Definitive Local Therapy for Adenocarcinoma of the Prostate

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to PSA progression [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Time to PSA progression will be compared in the two groups using a log-rank test.


Secondary Outcome Measures:
  • Proportion of patients who achieve complete response (by PSA) during the combination phase [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Proportion of patients with PSA progression during the combination phase [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Time to PSA nadir during the combination phase [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Time to PSA progression during the combination phase [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Time to PSA progression during the observation phase [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Proportion of patients with PSA progression during the observation phase [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Safety and tolerability assessed using NCI CTCAE version 4.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 78
Study Start Date: August 2010
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm I

Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.

COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.

Other: placebo
Given orally
Other Name: PLCB
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Given orally
Other Names:
  • R4733
  • RO4929097
Drug: bicalutamide
Given orally
Other Names:
  • Casodex
  • CDX
Experimental: Arm II

Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.

COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Given orally
Other Names:
  • R4733
  • RO4929097
Drug: bicalutamide
Given orally
Other Names:
  • Casodex
  • CDX

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed prostate cancer

    • Stage D0 OR D1 disease (i.e., tumor originally diagnosed as being limited to the prostate and regional lymph nodes)
    • Has a rising PSA value after definitive local therapy (i.e., prostatectomy or radiotherapy) and no radiographic evidence of disease
  • PSA progression after local treatment:

    • PSA values for patients after surgery must be ≥ 0.2 ng/mL, determined by two measurements, ≥ 1 month apart and ≥ 6 months after prostatectomy
    • PSA values for patients after radiotherapy must be ≥ 2.0 ng/mL above the nadir PSA achieved after radiotherapy, determined by two measurements at 1 month apart and ≥ 6 months after completion of the radiotherapy treatment (patients who received adjuvant or salvage radiotherapy after prostatectomy must have PSA of ≥ 0.2 ng/mL)
    • The first two PSA values, along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value)
  • No metastatic disease on baseline bone scan and CT scan of the abdomen/pelvis
  • ECOG performance status 0-2
  • Life expectancy ≥ 6 months
  • WBC ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 40 mL/min for patients with creatinine levels above normal
  • Bilirubin normal
  • AST and/or ALT ≤ 2.5 times ULN
  • Serum total testosterone level ≥ 150 ng/dL
  • No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation
  • Fertile patients must use two effective forms of contraception (i.e., barrier contraception and one other method of contraception) for 1 week before, during, and for ≥ 12 months after completion of study treatment
  • Able to swallow tablets
  • No malabsorption syndrome or other condition that would interfere with intestinal absorption
  • No uncontrolled concurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • A history of torsades de pointes
    • Cardiac arrhythmia other than chronic, stable atrial fibrillation
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • Baseline QTc ≤ 450 msec
  • No serologic positivity for acute hepatitis A, acute or chronic hepatitis B, or acute or chronic hepatitis C
  • No history of liver disease or other forms of hepatitis or cirrhosis
  • No HIV-positive patients on combination antiretroviral therapy
  • No serious concurrent systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or bicalutamide
  • Patients may not donate sperm or blood during or for ≥ 12 months after completion of study treatment
  • No concurrent medications or food that may interfere with the metabolism of RO4929097 including grapefruit and fresh-squeezed grapefruit juice
  • Recovered from adverse events to < CTCAE grade 2
  • At least 3 months since prior and no concurrent androgen-deprivation therapy (ADT)

    • Hormone-ablative treatment is only allowed in the neoadjuvant setting or in the setting of primary or salvage radiotherapy
    • No more than 36 months of neoadjuvant/ adjuvant ADT
  • More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior and no concurrent estrogens, estrogen-like substances (i.e., PC-SPES, saw palmetto, or other herbal product that may contain phytoestrogens), or any other hormonal therapy (including flutamide, nilutamide, finasteride, ketoconazole, systemic corticosteroids, megestrol acetate, or cyproterone acetate)
  • No other concurrent investigational agents
  • No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
  • No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4
  • No other investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy, including chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or surgery for cancer
  • No concurrent hormonal therapy with a leuteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix)
  • No concurrent growth factors (e.g., G-CSF), packed RBC transfusions, or platelet transfusions
  • No concurrent antiarrhythmics or other medications known to prolong QTc
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200810

Locations
United States, New Jersey
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Stein UMDNJ - Robert Wood Johnson University Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01200810     History of Changes
Other Study ID Numbers: NCI-2011-02527, CINJ-081001, CDR0000684276
Study First Received: September 10, 2010
Last Updated: May 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Bicalutamide
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014