Efficacy and Safety Study of Vandetanib (ZD 6474) in Combination With Bicalutamide Versus Bicalutamide Alone in Patients With Chemotherapy Naive Hormone Refractory Prostate Cancer.

NCT00757692 | Completed Phase 2

• 1 other identifier: OZM-011
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 4

Brief Summary

Purpose To define the efficacy, tolerability and safety of Vandetanib in combination with bicalutamide in patients with chemotherapy naive hormone refractory prostate cancer Hypothesis There will be a PSA response when Vandetanib is given in combination with Bicalutamide in Chemotherapy Naive Hormone refractory prostate cancer patients.

Conditions

Prostate Cancer

Keywords

Vandetanib (ZD6474); Hormone; Refractory; Prostate Cancer; Chemotherapy; Naïve

Outcome Measures

Primary Outcomes (1)

• PSA response

  Continuous to end of study

Secondary Outcomes (2)

• time to over all progression

  continuous

• Evaluation of treatment related toxicity

  continuous

Study Arms (2)

A

EXPERIMENTAL

Vandetanib at 300 mg in combination with Bicalutamide at 50 mg will be administered orally, daily and continuously

Drug: Vandetanib

B

ACTIVE COMPARATOR

Bicalutamide at 50 mg will be administered orally, daily and continuously.

Drug: Bicalutamide

Interventions

Vandetanib DRUG

Vandetanib at 300 mg in combination with Bicalutamide at 50 mg will be administered orally, daily and continuously

A

Bicalutamide DRUG

Bicalutamide at 50 mg will be administered orally, daily and continuously.

B

Eligibility Criteria

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

You may qualify if:

• Patients must have a pathological diagnosis of adenocarcinoma of the prostate
• Patients must have biochemically recurrent disease or metastatic disease that is asymptomatic or minimally symptomatic (total daily morphine dose \< 30mg.day) for which no curative therapy exists.
• Patients must have documented evidence od PSA progression while receiving androgen ablative therapy (i.e. must be hormone refractory). Progression is defined as the development of new metastatic lesions, or rising PSA defined as at least two rises in PSA at least 1 week apart. If the second PSA is not rising, a thrid PSA is required to show further increase; if not, a subsequent level must show further increase. The third (or subsequent) PSA confirming progression must be within 2 weeks of randomization.
• The PSA must be =\> 2ug/L at the time of study entry.
• ECOG performance status of 0 or 1
• Age =\>18 years
• Patients must have a life expectancy of at least 12 weeks
• No Prior chemotherapy is permissible for hormone refractory disease. Chemotherapy may have been received in a neoadjuvant or adjuvant setting provided it was given 12 months prior to registration.
• Hormone Therapy
• Prior hormone therapy in the form of either medical or surgical castration is required. If the patient is receiving medical androgen abalation a castrate level of testosterone (1.7nmol/L) must be present. Therapy with LHRH agonist must continue for those prostate cancer patients already receiving this treatment at the time of registration. If the patients has discontinued the LHRH agonist, this must be restarted and a castrate level of testosterone must be present.
• Prior use of nonsteroidal antiandrogens (including bicalutamide) is permitted but must have been discontinued 6 weeks prior to registration.
• Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed between the last dose and registration in the trial. Exceptions will be made for limited field, single fraction palliative radiation to bone.
• No concurrent treatment with steriods unless steriods have been ingested for 4 weeks prior to commencing study at a dose of less than or equal to an equivalent of prednisone 20mg per day.
• No concurrent experimental trial medication is permitted. No prior use of VEGF/VEGFR or EGFR targeting agents for hormone refractory disease is permitted.
• Laboratory Requirements- within 7 calendar days prior to registration Hematology: haemoglobin \>= 100g/L neutrophils \>=1.5 x 10(9)/L Platelets \>=100 x 10(9)/L INR =\<1.5 x upper limit of normal Biochemistry: AST, ALT = \<1.5 x upperlimit of normal Bilirubin \<1.5 x upper limit of normal Serum creatinine \<1.5 x upper limit of normal

You may not qualify if:

• Patients with a history of other invasive malignancy, except:adequately treated non melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for 3 years.
• Patients with known brain metastases or leptomemingeal disease are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of nerologic and other adverse events.
• History of allergic reactions and/or sensitivity attributed to compounds of similar chemical or biological composition to Vandetanib or other agents used in the study.
• Other serious intercurrent illness or medical condition that might be aggravated by protocol treatment including;myocardial infarction within 6 months prior to study entry, congestive heart failure, unstable angina,cardiomyopathy, unstable ventricular arrhythmias,OTc (Bazett's) \>480msec Uncontrolled hypertension (systolic \>160, diatolic \>100) Uncontrolled psychotic disorders, serious infections,peptic ulcer disease,history of bleeding diathesis
• Upper gasrtointerstinal or other conditions that would preclude compliance with oral medication
• Patients with immune deficiency are at increased risk of lethal infections when treated with Marrow-suppressive therapy. Therefore, HIV positive patients receiving combination ant-retroviral therapy are excluded from study because of possible risk of lethal infection and additionally because of the possible pharmacokinetic interactions with Vandetanib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
• Patients who require escalating amounts of narcotic therapy to control pain e.g. morphine equivalent dose \>30mg/day) since these patients would more appropriately be offered systemic chemotherapy
• Patients who require therapeutic anticoagulation with warfarin.
• Patients who require the following medication:concomittant use of warfarin, Class 1A antiarrythmics (e.g., quinidine, procainamide, disopyramide) Class
• C antiarrhythmics (e.g.,flecainide, propafenone), Class III antiarrhythmics (e.g., amiodarone, sotalol, ibutilide), antipsychotics (e.g., thioridazine, chlorpromazine, pimozide, haloperidol, droperidol), tri/tetracyclic antidepressants (e.g., amitriptyline, imipramine, maprotiline), ketoconazole, antiepileptics and macrolide antibiotics.
• Patients who cannot stop ingestion of grapefruit/juice.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• AstraZeneca: collaborator

Study Sites (4)

BC Cancer Agency - Centre for Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

vandetanib; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Kim Chi, MD

  BC Cancer Agency - Vancouver Centre

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 19, 2008
• First Posted: September 23, 2008
• Study Start: January 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 20, 2013

Record last verified: 2013-02

Locations

CA (4)