Everolimus as First-Line Therapy in Treating Patients With Prostate Cancer

NCT ID: NCT00976755

Last Updated: 2019-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-14
• Study Completion Date: 2019-08-08

Brief Summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying the side effects of everolimus and to see how well it works as first-line therapy in treating patients with prostate cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine the progression-free survival at 12 weeks of patients with non-rapidly progressive castration-resistant prostate cancer treated with everolimus as first-line therapy.
• Assess the activity and safety of this regimen in these patients.

Secondary

• Determine the progression-free survival at 24 weeks of patients treated with this regimen.
• Determine the percentage of PSA response from baseline to 12 weeks in patients treated with this regimen.
• Determine the changes in PSA-doubling time in patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up at 28 days and then every 3 months.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Everolimus

Everolimus:

10mg daily

Group Type: EXPERIMENTAL

everolimus

Intervention Type: DRUG

Everolimus:

10mg daily

Interventions

everolimus

Everolimus:

10mg daily

Intervention Type: DRUG

Other Intervention Names

Afinitor®; Votubia®; RAD001

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or locally advanced adenocarcinoma of the prostate

• No curative therapy available
• Oligosymptomatic or asymptomatic patients
• Tumor progression after ≥ 1 hormonal treatment (orchiectomy or luteinizing-hormone releasing-hormone [LHRH] agonist) with documented total testosterone levels ≤ 1.7 nmol/L (≤ 50 ng/dL)

• Concurrent LHRH agonist therapy is required for patients who have not been surgically castrated
• Must have stopped antiandrogen therapy ≥ 6 weeks before the start of trial treatment without withdrawal response
• PSA progression defined as an increase in PSA ≥ 25% (and an absolute increase of 2 ng/mL or more) over nadir value on hormonal therapy measured on 3 successive occasions ≥ 1 week apart

• If the third measurement is not higher than the second, a fourth measurement will be taken (patient allowed if the fourth measurement is higher than the second)
• PSA doubling time ≥ 55 days
• No known or suspected CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 90 g/L
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2.5 times ULN
• Creatinine clearance ≥ 40 mL/min
• Fasting serum cholesterol ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 times ULN

• Appropriate lipid-lowering medication allowed in case one or both of these thresholds are exceeded
• Patient compliance and geographic proximity that would allow proper staging and follow-up are required
• No malignancy within the past 5 years except curatively treated localized nonmelanoma skin cancer or Ta and Tis bladder cancer
• No known history of HIV
• No serologically confirmed hepatitis B or C
• No serious underlying medical condition that, in the judgment of the investigator, could impair the ability of the patient to participate in the trial including, but not limited to, any of the following conditions:

• Uncontrolled or acute severe infection
• Uncontrolled diabetes
• Advanced chronic obstructive pulmonary disease
• No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, or interfering with compliance for oral drug intake
• No known hypersensitivity to trial drug or hypersensitivity to any of its components

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy, radioisotopes, small molecules, immunotherapy, or investigational drug therapy for prostate cancer
• No local radiotherapy within the past 2 weeks
• No major surgery within the past 4 weeks
• No concurrent radiotherapy
• No concurrent angiotensin converting enzyme inhibitors
• No concurrent chronic immunosuppressive therapy including high-dose corticosteroids (i.e., > 25 mg prednisone equivalent per day)
• No products known to affect PSA levels (e.g., PC Calm, PC Plus, PC SPES, finasteride, or fluconazole) within the past 4 weeks or concurrently
• No strong CYP3A4 inhibitors (e.g., itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, or grapefruit or its juice) within the past 2 weeks or concurrently
• No strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, phenobarbital, or St. John wort) within the past 2 weeks or concurrently
• No concurrent bisphosphonates

• Patients must continue to receive bisphosphonates regularly if it was started prior to entering the trial
• No concurrent experimental drugs or other anticancer therapy in a clinical trial within the past 30 days
• No concomitant drugs contraindicated for use with the trial drug according to the investigator's drug brochure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arnoud Templeton, MD

Role: PRINCIPAL_INVESTIGATOR

Cantonal Hospital of St. Gallen

Silke Gillessen, MD

Role: STUDY_CHAIR

Cantonal Hospital of St. Gallen

Locations

Kantonspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Luzern

Lucerne, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

References

Templeton A, Rothermundt C, Cathomas R, et al.: Everolimus as first-line therapy in nonrapidly progressive metastatic castration-resistant prostate cancer (mCRPC): A multicenter phase II trial (SAKK 08/08). [Abstract] J Clin Oncol 29 (Suppl 15): A-4588, 2011.

Reference Type: RESULT

Templeton AJ, Dutoit V, Cathomas R, Rothermundt C, Bartschi D, Droge C, Gautschi O, Borner M, Fechter E, Stenner F, Winterhalder R, Muller B, Schiess R, Wild PJ, Ruschoff JH, Thalmann G, Dietrich PY, Aebersold R, Klingbiel D, Gillessen S; Swiss Group for Clinical Cancer Research (SAKK). Phase 2 trial of single-agent everolimus in chemotherapy-naive patients with castration-resistant prostate cancer (SAKK 08/08). Eur Urol. 2013 Jul;64(1):150-8. doi: 10.1016/j.eururo.2013.03.040. Epub 2013 Apr 6.

Reference Type: DERIVED

PMID: 23582881 (View on PubMed)

Other Identifiers

SWS-SAKK-08/08

Identifier Type: -

Identifier Source: secondary_id

EU-20967

Identifier Type: -

Identifier Source: secondary_id

CDR0000649049

Identifier Type: -

Identifier Source: secondary_id

SAKK 08/08

Identifier Type: -

Identifier Source: org_study_id