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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00976755
First received: September 11, 2009
Last updated: May 2, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: everolimus
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Everolimus First-line Therapy in Non-rapidly Progressive Castration Resistant Prostate Cancer (CRPC). A Multicenter Phase II Trial.

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Progression-free survival (PFS) at 12 weeks [ Time Frame: at 12 weeks ]
    PFS at 12 weeks is defined as the absence of disease progression or death at 12 weeks after start of treatment.


Secondary Outcome Measures:
  • PFS at 24 weeks [ Time Frame: at 24 weeks ]
    PFS at 24 weeks is defined as the absence of any disease progression or death at 24 weeks after start of treatment.

  • Progression-free survival [ Time Frame: from start of treatment until progression or death of any cause ]
    from start of treatment until progression or death of any cause, whereas it will be censored at the last follow-up visit or initiation of a different treatment.

  • Adverse events (AEs) according to NCI CTCAE v. 3.0 [ Time Frame: from start of treatment until progression or death of any cause ]
    All AEs will be assessed according to NCI CTCAE v3.0

  • PSA response [ Time Frame: 50% and 30%, best and at 12 weeks ]

    50% PSA response is defined as a decrease in PSA level of at least 50% (compared to baseline PSA).

    30% PSA response is defined as a decrease in PSA level of at least 30% (compared to baseline PSA).

    Best response is defined as the percentage of change in PSA from baseline to the maximum decline in PSA at any point under treatment.

    Response at 12 weeks is defined as the percentage of change in PSA from baseline to 12 weeks (or earlier for those patients who discontinue therapy, in this case last PSA values recorded should be taken).


  • Changes in PSA-doubling time [ Time Frame: Time points for later calculations include: after 12 weeks, after 24 weeks and at best PSA response ]
    PSA-DT is calculated by natural log of 2 divided by the slope of the relationship between the log of PSA and time of PSA measurement for each patient.

  • Tumor assessment of measurable disease according to RECIST v1.1 criteria [ Time Frame: The first assessment will be performed after 12 weeks of treatment, or earlier if clinically indicated. ]
    For patients with measurable disease at baseline RECIST v1.1 will be used to define CR, PR, SD and PD.

  • Tumor assessment of bone lesions [ Time Frame: at 12 weeks. ]
    Bone metastases can be assessed by radionuclide bone scan.


Enrollment: 37
Actual Study Start Date: September 14, 2009
Estimated Study Completion Date: December 31, 2017
Primary Completion Date: November 29, 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Everolimus

Everolimus:

10mg daily

Drug: everolimus

Everolimus:

10mg daily

Other Names:
  • Afinitor®
  • Votubia®
  • RAD001

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.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00976755

Locations
Switzerland
Kantonspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, 5404
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Inselspital Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Kantonsspital Graubuenden
Chur, Switzerland, 7000
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Luzern
Luzern, Switzerland, 6000
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Kantonsspital Winterthur
Winterthur, Switzerland, 8401
UniversitaetsSpital Zuerich
Zurich, Switzerland, 8091
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Principal Investigator: Arnoud Templeton, MD Cantonal Hospital of St. Gallen
Study Chair: Silke Gillessen, MD Cantonal Hospital of St. Gallen
  More Information

Publications:
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00976755     History of Changes
Other Study ID Numbers: SAKK 08/08
SWS-SAKK-08/08
EU-20967
CDR0000649049
Study First Received: September 11, 2009
Last Updated: May 2, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
adenocarcinoma of the prostate
hormone-resistant prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on May 22, 2017