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

NCT00976755 | Completed Phase 2

• 4 other identifiers: SAKK 08/08SWS-SAKK-08/08EU-20967CDR0000649049
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 13

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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; hormone-resistant prostate cancer; stage III prostate cancer; stage IV prostate cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) at 12 weeks

  PFS at 12 weeks is defined as the absence of disease progression or death at 12 weeks after start of treatment.

  at 12 weeks

Secondary Outcomes (7)

• PFS at 24 weeks

  at 24 weeks

• Progression-free survival

  from start of treatment until progression or death of any cause

• Adverse events (AEs) according to NCI CTCAE v. 3.0

  from start of treatment until progression or death of any cause

• PSA response

  50% and 30%, best and at 12 weeks

• Changes in PSA-doubling time

  Time points for later calculations include: after 12 weeks, after 24 weeks and at best PSA response

Study Arms (1)

Arm A: Everolimus

EXPERIMENTAL

Everolimus: 10mg daily

Drug: everolimus

Interventions

everolimus DRUG

Everolimus: 10mg daily

Also known as: Afinitor®, Votubia®, RAD001

Arm A: Everolimus

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (13)

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6000, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (2)

• 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.

  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.

  PMID: 23582881 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Arnoud Templeton, MD

  Cantonal Hospital of St. Gallen

  PRINCIPAL INVESTIGATOR

• Silke Gillessen, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 14, 2009
• Study Start: September 14, 2009
• Primary Completion: November 29, 2012
• Study Completion: August 8, 2019
• Last Updated: August 9, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (13)