Hormone Refractory Prostate CancerPhase 2NCT01260688
Cediranib Maleate With or Without Dasatinib in Patients With HRPC-Resistant to Treatment With Docetaxel
A Phase 2 study testing cediranib maleate and dasatinib in people with Hormone Refractory Prostate Cancer and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 8 sites in 2 countries.
Trial summary
This randomized phase II trial is studying the side effects and how well giving cediranib maleate together with or without dasatinib works in treating patients with hormone-resistant prostate cancer resistant to treatment with docetaxel. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hormone Refractory Prostate Cancer, Recurrent Prostate Cancer
- What is being tested?
- cediranib maleate and dasatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Oct 2010to Feb 2014
- 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/cytologically confirmed prostate cancer
- Measurable/non-measurable disease
- Prior hormonal therapy with medical LHRH agonist or orchiectomy castration (Castrate level of testosterone (< 50 ng/dL) required)
- Clinical/radiographic evidence of progression on or after docetaxel therapy
- No active pleural/pericardial effusion of any grade
- No meningeal metastases/untreated known brain metastases
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- Patients with treated brain metastasis with radiologic, clinical evidence of stability, with no evidence of cavitation/hemorrhage in the brain lesions allowed if asymptomatic and not requiring corticosteroids
- Life expectancy >3 months
- ECOG PS 0-2 (Karnofsky PS 60-100%)
- ANC >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 9 g/dL
- INR=< 1.3
- Total bilirubin =< 1.25 times ULN
- AST and ALT=< 2.0 times ULN (5 x ULN if clearly attributable to liver metastasis)
- Creatinine normal OR creatinine clearance >= 60 mL/min
- LVEF> institutional normal range by ECHO/MUGA
- Urine dipstick for protein < 1+ OR < 1 g on 24-hour urine collection
Who cannot join
- >5 years since any malignancy except in situ cancer, non-metastatic basal/squamous cell skin cancer, or other cancer for which the patient has been curatively treated
- Fertile patients must use effective contraception
- No condition that impairs ability to swallow/absorb
- No history of allergic reactions attributed to compounds of similar chemical/biologic composition to cediranib/dasatinib
- No systolic BP>150 mmHg and/or diastolic BP>100 mmHg
- QTc prolongation (>=480 msec by Fridericia correction) or other significant ECG abnormalities are ineligible
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- No active/uncontrolled infections, serious illness, or medical conditions that would not permit patient to be managed according to protocol
- No known immunodeficiency syndrome
- No clinical/radiological evidence of severe/uncontrolled interstitial lung disease
- No history/concurrent idiopathic pulmonary fibrosis
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No unresolved toxicity>=CTCAE grade 2 (except alopecia) from prior anticancer therapy
- 4 weeks since prior anti-androgens
- 4 weeks since prior chemotherapy following docetaxel for metastatic disease (Any number of regimens allowed)
- 4 weeks since prior hormonal therapy or abiraterone
- 3 weeks since prior radioisotopes or radiotherapy and recovered
- No prior therapy with angiogenesis or Src or FAK inhibitors
- 3 weeks since prior major surgery and recovered
- 1 week since prior corticosteroids
- Concurrent zoledronic acid allowed provided patient has been receiving it prior to start of study treatment
- Concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of cediranib and dasatinib will be determined following review of their case by the principal investigator or co-investigator
- 14 days before and after study and no concurrent CYP3A4-active agents or substances (including strong inhibitors or inducers)
- Concurrent prophylactic low-dose warfarin (INR must be close monitored) or low-molecular weight heparin allowed
- No other concurrent investigational agents
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States5 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins University
Baltimore, Maryland, 21287-8936
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, 46845
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, 60702
Canada3 sites
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: A Phase 2 Randomized Study of Cediranib (AZD2171) Alone Compared With the Combination of Cediranib (AZD2171) Plus BMS-354825 (Dasatinib, Sprycel) in Docetaxel Resistant, Castration Resistant Prostate Cancer
This randomized phase II trial is studying the side effects and how well giving cediranib maleate together with or without dasatinib works in treating patients with hormone-resistant prostate cancer resistant to treatment with docetaxel. Cediranib maleate and dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving cediranib maleate together with dasatinib or alone is an effective treatment for prostate cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the progression-free survival of patients with docetaxel-resistant and castration-resistant prostate cancer treated with cediranib maleate with versus without dasatinib.
SECONDARY OBJECTIVES:
- To confirm the safety and tolerability of cediranib maleate with versus without dasatinib in these patients.
II. To calculate objective response rates of cediranib maleate with versus without dasatinib, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in patients with measurable disease at baseline.
III. To perform symptom assessment using the FACT-P questionnaire and the Present Pain Intensity (PPI) scale from the McGill-Melzack questionnaire.
IV. To explore bone resorption markers (e.g., c-telopeptide and bone alkaline phosphatase), and to correlate these biomarkers with clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to the presence of soft tissue (visceral or nodal) vs bone-only disease. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study, patients are followed up for 4 weeks.
- Being tested
- cediranib maleate, dasatinib
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cediranib maleateDrug
Also called Recentin
Given orally
dasatinibDrug
Also called BMS-354825
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: cediranib maleate; Drug: dasatinib |
| Arm II | Experimental | Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: cediranib maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
Progression is defined using the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, which includes a compilation of prostate-specific antigen (PSA), bone scan, and CT-scan assessments (Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 3 months
Secondary outcomes (14)
Number of Participants With Toxicities
Incidence of toxicities graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.0
Measured: Up to 30 days after last dose of study drugs
Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale
Present Pain Intensity (PPI) scale. Scale is measured 0-5, where 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain and 5=excruciating pain Participants who were up to completing the assessment (did not decline) and who reported a score >=2 at the end of any cycle are reported.
Measured: After every cycle (median duration on study = 4 cycles)
Number Who Experienced Study Medication Dose Intensity
Number of patients who experienced study medication dose of over 80% during Cycle 1 was assessed.
Measured: Cycle 1 (an average of 28 days)
Treatment Discontinuation
Discontinuation of treatment in cycle 1 (average of 28 days)
Measured: Cycle 1 (average of 28 days)
Treatment Discontinuation Due to Adverse Events (AEs)
Treatment discontinuation due to Adverse Events
Measured: Through study completion (median duration on study = 4 cycles)
Non-AE Related Treatment Discontinuation
Non-Adverse Event related Treatment Discontinuation
Measured: Through study completion (median duration on study = 4 cycles)
Overall Response Rate
Best overall response rate of each evaluable patient
Measured: Duration of Study (median duration on study = 4 cycles)
Treatment Related Deaths
Number of treatment related deaths
Measured: Through study completion (median duration on study = 4 cycles)
Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced
Participants for which beta-C telopeptide was reduced
Measured: Through study completion (median duration on study = 4 cycles)
Number of Participants With Increased Alkaline Phosphatase BAP
Number of participants with increased alkaline phosphatase BAP
Measured: Through study completion (median duration on study = 4 cycles)
Dose Interruption Due to AEs
The number of participants with dose-interruptions in each arm due to adverse events
Measured: Through study completion (median duration on study = 4 cycles)
Dose Reductions
The number of participants with dose reductions in each arm
Measured: Duration of Study (median duration on study = 4 cycles)
Overall Response Rate
Response Rate of Stable Disease and Progressive Disease
Measured: Duration of Study (median duration on study = 4 cycles)
Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Scale is measured on a range from 0 (worst quality of life) to 156 (best quality of life).
Measured: Up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2010 (estimated)
- Study startOct 2010
- Primary completionJan 2013
- Study completionFeb 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hormone Refractory Prostate CancerStudies 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
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sebastien Hotte, Principal investigator, University Health Network-Princess Margaret Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01260688
- Sponsor's protocol ID
- NCI-2011-02544
- Other IDs
- PMH-PJC-002, PJC-002, 8476, U01CA070095, U01CA132123, N01CM00071
- Status last verified
- Jul 2018
- First submitted
- 14 Dec 2010
- Last updated
- 8 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Spreafico A, Chi KN, Sridhar SS, Smith DC, Carducci MA, Kavsak P, Wong TS, Wang L, Ivy SP, Mukherjee SD, Kollmannsberger CK, Sukhai MA, Takebe N, Kamel-Reid S, Siu LL, Hotte SJ. A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients. Invest New Drugs. 2014 Oct;32(5):1005-16. doi: 10.1007/s10637-014-0106-5. Epub 2014 May 3.
PubMed 24788563
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized Study of Cediranib (AZD2171) Alone Compared With the Combination of Cediranib (AZD2171) Plus BMS-354825 (Dasatinib, Sprycel) in Docetaxel Resistant, Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT01260688
- Acronym / sponsor ID
- NCI-2011-02544
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 15 Dec 2010 (estimated)
- Results
- Posted 5 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial is studying the side effects and how well giving cediranib maleate together with or without dasatinib works in treating patients with hormone-resistant prostate cancer resistant to treatment with docetaxel. Cediranib maleate and dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving cediranib maleate together with dasatinib or alone is an effective treatment for prostate cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the progression-free survival of patients with docetaxel-resistant and castration-resistant prostate cancer treated with cediranib maleate with versus without dasatinib.
SECONDARY OBJECTIVES:
- To confirm the safety and tolerability of cediranib maleate with versus without dasatinib in these patients.
II. To calculate objective response rates of cediranib maleate with versus without dasatinib, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in patients with measurable disease at baseline.
III. To perform symptom assessment using the FACT-P questionnaire and the Present Pain Intensity (PPI) scale from the McGill-Melzack questionnaire.
IV. To explore bone resorption markers (e.g., c-telopeptide and bone alkaline phosphatase), and to correlate these biomarkers with clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to the presence of soft tissue (visceral or nodal) vs bone-only disease. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study, patients are followed up for 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: cediranib maleate, Drug: dasatinibPatients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm II | Experimental | Drug: cediranib maleatePatients receive cediranib maleate as in arm I. Courses repeat every 28 days 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 (18 listed)
- Histologically/cytologically confirmed prostate cancer
- Measurable/non-measurable disease
- Prior hormonal therapy with medical LHRH agonist or orchiectomy castration (Castrate level of testosterone (< 50 ng/dL) required)
- Clinical/radiographic evidence of progression on or after docetaxel therapy
- No active pleural/pericardial effusion of any grade
Key exclusion criteria (24 listed)
- >5 years since any malignancy except in situ cancer, non-metastatic basal/squamous cell skin cancer, or other cancer for which the patient has been curatively treated
- Fertile patients must use effective contraception
- No condition that impairs ability to swallow/absorb
- No history of allergic reactions attributed to compounds of similar chemical/biologic composition to cediranib/dasatinib
- No systolic BP>150 mmHg and/or diastolic BP>100 mmHg
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 |
|---|---|---|
| cediranib maleateAlso: RecentinGiven orally | Drug | Arm I, Arm II |
| dasatinibAlso: BMS-354825Given orally | Drug | Arm I |
Primary outcome
12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
Time frame: 3 months
Progression is defined using the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, which includes a compilation of prostate-specific antigen (PSA), bone scan, and CT-scan assessments (Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
14 secondary outcomes
Number of Participants With Toxicities
Time frame: Up to 30 days after last dose of study drugs
Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale
Time frame: After every cycle (median duration on study = 4 cycles)
Number Who Experienced Study Medication Dose Intensity
Time frame: Cycle 1 (an average of 28 days)
Treatment Discontinuation
Time frame: Cycle 1 (average of 28 days)
Treatment Discontinuation Due to Adverse Events (AEs)
Time frame: Through study completion (median duration on study = 4 cycles)
Non-AE Related Treatment Discontinuation
Time frame: Through study completion (median duration on study = 4 cycles)
Overall Response Rate
Time frame: Duration of Study (median duration on study = 4 cycles)
Treatment Related Deaths
Time frame: Through study completion (median duration on study = 4 cycles)
Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced
Time frame: Through study completion (median duration on study = 4 cycles)
Number of Participants With Increased Alkaline Phosphatase BAP
Time frame: Through study completion (median duration on study = 4 cycles)
Dose Interruption Due to AEs
Time frame: Through study completion (median duration on study = 4 cycles)
Dose Reductions
Time frame: Duration of Study (median duration on study = 4 cycles)
Overall Response Rate
Time frame: Duration of Study (median duration on study = 4 cycles)
Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Time frame: Up to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24788563Spreafico A, Chi KN, Sridhar SS, Smith DC, Carducci MA, Kavsak P, Wong TS, Wang L, Ivy SP, Mukherjee SD, Kollmannsberger CK, Sukhai MA, Takebe N, Kamel-Reid S, Siu LL, Hotte SJ. A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients. Invest New Drugs. 2014 Oct;32(5):1005-16. doi: 10.1007/s10637-014-0106-5. Epub 2014 May 3.
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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.
Sebastien Hotte principal investigator
University Health Network-Princess Margaret Hospital
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cediranib maleate and dasatinib in people with Hormone Refractory Prostate Cancer and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 8 sites in 2 countries.
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 18 inclusion and 24 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: finished, as of the sponsor's last update on 8 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada. 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. 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 5 Dec 2013). 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?
12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01260688, which also lists 1 linked publication.
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 8 Aug 2018; AzTrials last refreshed its copy on 8 Nov 2026.