CESAR Study in Prostate Cancer With Temsirolimus Added to Standard Docetaxel Therapy (CEPTAS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Central European Society for Anticancer Drug Research
Sponsor:
Information provided by (Responsible Party):
Central European Society for Anticancer Drug Research
ClinicalTrials.gov Identifier:
NCT01206036
First received: August 17, 2010
Last updated: September 7, 2012
Last verified: September 2012
  Purpose

In this Phase I study safety of the combination of Docetaxel and Temsirolimus needs to be shown before the study can be expanded into a Phase II study to examine the activity of a safe combination of Temsirolimus and Docetaxel in a comparison with Docetaxel alone.


Condition Intervention Phase
Prostatic Neoplasms
Drug: Docetaxel
Drug: Temsirolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study With Temsirolimus Versus no add-on in Patients With Castration Resistant Prostate Cancer (CRPC) Receiving First-line Docetaxel Chemotherapy

Resource links provided by NLM:


Further study details as provided by Central European Society for Anticancer Drug Research:

Primary Outcome Measures:
  • recommended dose [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
    Phase I Part: Primary endpoint is the Recommended Dose (RD) for the Phase II Part chosen between the three DLs based on the dose escalation scheme.

  • disease progression-free survival [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Phase II Part: Primary endpoint is to evaluate the activity of the addition of Temsirolimus to standard treatment on the disease progression-free survival (DPFS Chemotherapy) in patients with castration resistant prostate cancer receiving first-line Docetaxel chemotherapy.


Secondary Outcome Measures:
  • safety as defined as occurence of treatment related adverse events [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
    Phase I Part: Secondary endpoint is the collection of safety data on the dose levels used in this part.

  • overall response [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: Responses of measurable disease (RECIST 1.1 criteria) including the overall response rate (RR, CFR+PR) and the disease control rate (PR+CR+SD). In addition to the overall response rate RR, the trial will also evaluate the number of responders based on PSA evaluation only (RR-PSA) and the number of responders based on RECIST evaluation only (RR-RECIST) among those who are evaluable by that criterion, respectively. RR is only evaluated for the chemotherapy part of the Phase II part of the trial.

  • 1-year Disease-Progression Free Survival Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: 1-year Disease-Progression Free Survival Rate (DPFS-1yR); defined as the quotient defined exactly in the same way as DPFS-6mR with the landmark time point equal to 1 year, +/- 4 weeks for assessment one year after randomization.

  • DPFS time [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: DPFS time measured as failure time between 1st randomization and disease progression or death whatever occurred first. Patients lost-to follow-up, dropping out (e.g. when withdrawing consent) or patients surviving progression free at the end-of-study time point are treated as censored cases.

  • TTP-PSA [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: Time to PSA progression (TTP-PSA) measured from randomization until PSA progression as defined in Scher et al. "Decline from baseline: record time from start of therapy to first PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later (ie, a confirmed rising trend)†"

  • toxicity based on treatment-related toxicities using CTCAE v4.0 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Phase II Part: Evaluation of toxicity using CTCAE v4.0

  • PSA [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: Proportion of patients with drop of PSA of > 30% in the evaluation period compared to baseline compared to baseline.

  • quality of life [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: Quality of life using the EORTC questionnaire

  • overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: overall survival (OS) measured from randomization until death or lost to follow up (censored survival time)

  • Frequency of medication for pain [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase II Part: Frequency of medication for pain


Estimated Enrollment: 18
Study Start Date: July 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Docetaxel
    DL 1: Docetaxel 60mg/m^2, Temsirolimus 15mg. DL 2: Docetaxel 60mg/m^2, Temsirolimus 25mg. DL 3: Docetaxel 75mg/m^2, Temsirolimus 25mg. One cycle is defined as a 3 week period (21 days) where docetaxel is given on day 1, and temsirolimus on days 1, 8 and 15.
    Other Name: Taxotere
    Drug: Temsirolimus
    DL 1: Docetaxel 60mg/m^2, Temsirolimus 15mg. DL 2: Docetaxel 60mg/m^2, Temsirolimus 25mg. DL 3: Docetaxel 75mg/m^2, Temsirolimus 25mg. One cycle is defined as a 3 week period (21 days) where docetaxel is given on day 1, and temsirolimus on days 1, 8 and 15.
    Other Name: Torisel
Detailed Description:

The purpose of this Phase I study is to evaluate feasibility of dose levels DL1, DL2 and DL3 (which are combinations of Temsirolimus and Docetaxel) and defining a recommended dose (RD) for the Phase II part using these dose levels in a dose escalating scheme.

Secondary objectives are the collection of safety data on the dose levels used in this part.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria Phase I Part:

  • Adult males ≥18 years of age.
  • Patients with CRPC defined as confirmed rise of PSA levels after orchiectomy or LHRH agonist based therapy.
  • Progressive disease, defined as PSA progression by confirmed rising PSA levels.
  • PSA at time of study entry ≥2ng/ml within 1 week prior to treatment (according to Scher 2008).
  • Bone metastasis and/or lymph node and/or visceral organ metastases allowed. Measurable and non measurable disease allowed.
  • Performance status (PS) 0-1 ECOG.
  • Signed written informed consent.
  • White blood cell count (WBC) ≥4x10^9/L with neutrophils ≥1.5x10^9/L, platelet count ≥100x10^9/L, hemoglobin ≥9g/dL.
  • Total bilirubin <=2 x upper limit of normal.
  • AST and ALT <=2.5 x upper limit of normal, or <=5 x upper limit of normal in case of liver metastases.
  • Serum creatinine <=1.5 x upper limit of normal or creatinine clearance > 60 ml/min.
  • Androgen ablation will have to be continued. Antiandrogens such as bicalutamide will have to be discontinued at least 4 weeks prior to the start of study treatment.

Exclusion Criteria Phase I Part:

  • Clinically symptomatic brain or meningeal metastasis.
  • Receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
  • Any investigational drug within the 30 days before inclusion.
  • Not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy, as judged by the investigator.
  • Nonhealing wound or ulcer.
  • Grade ≥ 3 hemorrhage within the past month.
  • Any condition / concomitant disease not allowing chemotherapy with docetaxel, prednisone and temsirolimus in the discretion of the treating physician, like: Renal insufficiency requiring dialyses; congestive heart failure or uncontrolled angina pectoris; prior myocardial infarction within 6 months of start of chemotherapy; uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs) or arrhythmias; instable diabetes mellitus, ulceration from diabetes mellitus or other conditions not allowing high dose corticosteroids; effusions in pericardium, pleura or abdomen symptomatic and in need of being punctured.
  • Known hypersensitivity to any of the components in the temsirolimus infusion or other medical reasons for not being able to receive adequate premedication (antihistamine agents).
  • Legal incapacity or limited legal capacity
  • Medical or psychological conditions that would not permit the patient to
  • complete the study or sign informed consent.

Inclusion Criteria Phase II Part, Chemotherapy Period:

  • Adult males ≥ 18 years of age.
  • Patients with CRPC defined as confirmed rise of PSA levels after orchiectomy or LHRH agonist based therapy
  • Progressive disease, defined as PSA progression by confirmed rising PSA levels
  • PSA at time of study entry ≥ 2ng/ml within 1 week prior to treatment (according to Scher 2008).
  • Bone metastasis and/or lymph node and/or visceral organ metastases allowed. Measurable and non measurable disease allowed.
  • Performance status (PS) 0-1 ECOG.
  • Signed written informed consent.
  • White blood cell count (WBC) ≥4x10^9/L with neutrophils ≥1.5x10^9/L, platelet count ≥100x10^9/L, hemoglobin ≥9g/dL.
  • Total bilirubin <= 2 x upper limit of normal.
  • AST and ALT <=2.5 x upper limit of normal, or <=5 x upper limit of normal in case of liver metastases.
  • Serum creatinine <=1.5 x upper limit of normal or creatinine clearance >60 ml/min.
  • Androgen ablation will have to be continued. Antiandrogens such as bicalutamide will have to be discontinued at least 4 weeks prior to the start of study treatment.

Exclusion Criteria Phase II Part, Chemotherapy Period:

  • Prior Chemotherapy.
  • Clinically symptomatic brain or meningeal metastasis.
  • Receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
  • Any investigational drug within the 30 days before inclusion.
  • Not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy, as judged by the investigator.
  • Nonhealing wound or ulcer.
  • Grade ≥ 3 hemorrhage within the past month.
  • Any condition / concomitant disease not allowing chemotherapy with docetaxel, prednisone and temsirolimus in the discretion of the treating physician, like: Renal insufficiency requiring dialyses; congestive heart failure or uncontrolled angina pectoris; prior myocardial infarction within 6 months of start of chemotherapy; uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs) or arrhythmias; instable diabetes mellitus, ulceration from diabetes mellitus or other conditions not allowing high dose corticosteroids; effusions in pericardium, pleura or abdomen symptomatic and in need of being punctured.
  • Known hypersensitivity to any of the components in the temsirolimus infusion or other medical reasons for not being able to receive adequate premedication (antihistamine agents).
  • Legal incapacity or limited legal capacity.
  • Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.

Inclusion Criteria Phase II Part, Maintenance Period:

  • Completed 8 cycles (up to 26 weeks) treatment in Arm A
  • White blood cell count (WBC) ≥4x10^9/L with neutrophils ≥1.5x10^9/L, platelet count ≥100x10^9/L, hemoglobin ≥9g/dL.
  • Total bilirubin <=2 x upper limit of normal.
  • AST and ALT <=2.5 x upper limit of normal, or <=5 x upper limit of normal in case of liver metastases.
  • Serum creatinine <=1.5 x upper limit of normal or creatinine clearance >60 ml/min.
  • General condition sufficient to allow therapy with temsirolimus.
  • Signed Informed Consent.

Exclusion Criteria Phase II Part, Maintenance Period:

  • Disease Progression in the first 8 cycles (up to 26 weeks).
  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: NCT01206036

Contacts
Contact: Berta Moritz, PhD +43 1 522 3093 ext 10 berta.moritz@cesar.or.at

Locations
Germany
CESAR Study Center Recruiting
Essen, Germany
CESAR Study Center Recruiting
Freiburg, Germany
Sponsors and Collaborators
Central European Society for Anticancer Drug Research
Investigators
Study Chair: Rudolf Morant, MD Tumor-und Brustzentrum ZeTuP, St. Gallen, Switzerland
  More Information

Additional Information:
No publications provided

Responsible Party: Central European Society for Anticancer Drug Research
ClinicalTrials.gov Identifier: NCT01206036     History of Changes
Other Study ID Numbers: C-II-007, 2010-018370-21
Study First Received: August 17, 2010
Last Updated: September 7, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Central European Society for Anticancer Drug Research:
castration
prostate cancer
castration resistant prostate cancer
PSA
Docetaxel
Temsirolimus
disease progression free survival
DPFS
dose escalation

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

ClinicalTrials.gov processed this record on July 26, 2014