Clinical trial NCT00976755: Everolimus as First-Line Therapy in Treating Patients With Prostate Cancer
Official title: Everolimus First-line Therapy in Non-rapidly Progressive Castration Resistant Prostate Cancer (CRPC). A Multicenter Phase II Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
hormone-resistant prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2009-09-14
Enrollment: 37
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression-free survival (PFS) at 12 weeks
timeFrame: at 12 weeks
Secondary outcomes:
measure: PFS at 24 weeks
timeFrame: at 24 weeks
measure: Progression-free survival
timeFrame: from start of treatment until progression or death of any cause
measure: Adverse events (AEs) according to NCI CTCAE v. 3.0
timeFrame: from start of treatment until progression or death of any cause
measure: PSA response
timeFrame: 50% and 30%, best and at 12 weeks
measure: Changes in PSA-doubling time
timeFrame: Time points for later calculations include: after 12 weeks, after 24 weeks and at best PSA response
measure: Tumor assessment of measurable disease according to RECIST v1.1 criteria
timeFrame: The first assessment will be performed after 12 weeks of treatment, or earlier if clinically indicated.
measure: Tumor assessment of bone lesions
timeFrame: at 12 weeks.
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Luzern
country: Switzerland
facility: Kantonsspital Luzern
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Cantonal Hospital of St. Gallen
name: Arnoud Templeton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cantonal Hospital of St. Gallen
name: Silke Gillessen, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.