Adenocarcinoma of the ProstatePhase 2NCT01200810
Bicalutamide and RO4929097 in Treating Patients With Previously Treated Prostate Cancer
A Phase 2 study testing gamma-secretase/Notch signalling pathway inhibitor RO4929097 and bicalutamide in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer
- What is being tested?
- gamma-secretase/Notch signalling pathway inhibitor RO4929097 and bicalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Nov 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 50Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
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
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
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the difference in the time to PSA progression in patients with adenocarcinoma of the prostate who have rising PSA after definitive local therapy treated with bicalutamide with vs without gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097).
SECONDARY OBJECTIVES:
- To determine the proportion of patients from each arm who achieve complete response (by PSA) during the combination phase.
II. To determine the proportion of patients from each arm with PSA progression during the combination phase.
III. To determine the time to PSA nadir during the combination phase for patients in each arm.
IV. To determine the time to PSA progression during the combination phase for patients in each arm.
- To determine the time to PSA progression during the observation phase. VI. To determine the proportion of patients with PSA progression during the observation phase.
VII. To assess the safety and tolerability of gamma-secretase inhibitor RO4929097 in combination with bicalutamide.
VIII. To evaluate expression for targets of gamma secretase inhibitor in a prostate tissue microarray.
IX. To collect serum for future evaluation of soluble markers of gamma-secretase inhibition and angiogenesis.
OUTLINE: This is a multicenter study.
INDUCTION PHASE: All patients receive induction therapy comprising oral bicalutamide once daily for at least 16 weeks. Patients whose PSA declines at least 50% continue to the randomization phase.
RANDOMIZATION PHASE: Patients are stratified according to prior therapy (radiotherapy vs surgery) and randomized to 1 of 2 treatment arms.
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.
ARM II: Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO4929097 (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.
Patients with no disease progression continue to the combination phase. Patients with disease progression undergo imaging studies to verify the absence of metastatic disease before continuing to the combination phase.
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.
Blood and tumor tissue samples may be collected periodically for correlative studies. After completion of study treatment, patients are followed up every 6 weeks for 12 months.
- Being tested
- placebo, gamma-secretase/Notch signalling pathway inhibitor RO4929097, bicalutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboOther
Also called PLCB
Given orally
gamma-secretase/Notch signalling pathway inhibitor RO4929097Drug
Also called R4733, RO4929097
Given orally
bicalutamideDrug
Also called Casodex, CDX
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Placebo comparator | 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. Receives: Other: placebo; Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Drug: bicalutamide |
| Arm II | Experimental | 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. Receives: Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Drug: bicalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to PSA Progression
Time to PSA progression will be compared in the two groups using a log-rank test for a maximum of 54 weeks.
Measured: Up to 12 months
Secondary outcomes (7)
Proportion of Patients Who Achieve Complete Response (by PSA) During the Combination Phase
Measured: Up to 12 months
Proportion of Patients With PSA Progression During the Combination Phase
Measured: Up to 12 months
Time to PSA Nadir During the Combination Phase
Measured: Up to 12 months
Time to PSA Progression During the Combination Phase
Measured: Up to 12 months
Time to PSA Progression During the Observation Phase
Measured: Up to 12 months
Proportion of Patients With PSA Progression During the Observation Phase
Measured: Up to 12 months
Safety and Tolerability Assessed Using NCI CTCAE Version 4.0
Number of participants randomized to RO4929097 arm who experienced serious adverse events .
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2010 (estimated)
- Study startAug 2010
- Primary completionAug 2012
- Study completionNov 2012
Why it stopped: Drug was no longer available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma of the ProstateStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Stein, Principal investigator, UMDNJ - Robert Wood Johnson University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01200810
- Sponsor's protocol ID
- NCI-2011-02527
- Other IDs
- CINJ-081001, CDR0000684276
- Status last verified
- Oct 2017
- First submitted
- 10 Sep 2010
- Last updated
- 2 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01200810
- Acronym / sponsor ID
- NCI-2011-02527
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug was no longer available
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 14 Sep 2010 (estimated)
- Results
- Posted 23 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
PRIMARY OBJECTIVES:
- To determine the difference in the time to PSA progression in patients with adenocarcinoma of the prostate who have rising PSA after definitive local therapy treated with bicalutamide with vs without gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097).
SECONDARY OBJECTIVES:
- To determine the proportion of patients from each arm who achieve complete response (by PSA) during the combination phase.
II. To determine the proportion of patients from each arm with PSA progression during the combination phase.
III. To determine the time to PSA nadir during the combination phase for patients in each arm.
IV. To determine the time to PSA progression during the combination phase for patients in each arm.
- To determine the time to PSA progression during the observation phase. VI. To determine the proportion of patients with PSA progression during the observation phase.
VII. To assess the safety and tolerability of gamma-secretase inhibitor RO4929097 in combination with bicalutamide.
VIII. To evaluate expression for targets of gamma secretase inhibitor in a prostate tissue microarray.
IX. To collect serum for future evaluation of soluble markers of gamma-secretase inhibition and angiogenesis.
OUTLINE: This is a multicenter study.
INDUCTION PHASE: All patients receive induction therapy comprising oral bicalutamide once daily for at least 16 weeks. Patients whose PSA declines at least 50% continue to the randomization phase.
RANDOMIZATION PHASE: Patients are stratified according to prior therapy (radiotherapy vs surgery) and randomized to 1 of 2 treatment arms.
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.
ARM II: Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO4929097 (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.
Patients with no disease progression continue to the combination phase. Patients with disease progression undergo imaging studies to verify the absence of metastatic disease before continuing to the combination phase.
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.
Blood and tumor tissue samples may be collected periodically for correlative studies. After completion of study treatment, patients are followed up every 6 weeks for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Placebo comparator | Other: placebo, Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097, Drug: bicalutamidePatients 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. |
| Arm II | Experimental | Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097, Drug: bicalutamidePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (50 listed)
- Histologically confirmed prostate cancer
- PSA progression after local treatment:
- No metastatic disease on baseline bone scan and CT scan of the abdomen/pelvis
- ECOG performance status 0-2
- Life expectancy ≥ 6 months
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboAlso: PLCBGiven orally | Other | Arm I |
| gamma-secretase/Notch signalling pathway inhibitor RO4929097Also: R4733, RO4929097Given orally | Drug | Arm I, Arm II |
| bicalutamideAlso: Casodex, CDXGiven orally | Drug | Arm I, Arm II |
Primary outcome
Time to PSA Progression
Time frame: Up to 12 months
Time to PSA progression will be compared in the two groups using a log-rank test for a maximum of 54 weeks.
7 secondary outcomes
Proportion of Patients Who Achieve Complete Response (by PSA) During the Combination Phase
Time frame: Up to 12 months
Proportion of Patients With PSA Progression During the Combination Phase
Time frame: Up to 12 months
Time to PSA Nadir During the Combination Phase
Time frame: Up to 12 months
Time to PSA Progression During the Combination Phase
Time frame: Up to 12 months
Time to PSA Progression During the Observation Phase
Time frame: Up to 12 months
Proportion of Patients With PSA Progression During the Observation Phase
Time frame: Up to 12 months
Safety and Tolerability Assessed Using NCI CTCAE Version 4.0
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Stein principal investigator
UMDNJ - Robert Wood Johnson University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gamma-secretase/Notch signalling pathway inhibitor RO4929097 and bicalutamide in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 50 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to PSA Progression (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.