Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00004093

Trial Description

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Title

Phase I/II Study With Temsirolimus Versus no add-on in Patients With Castration Resistant Prostate Cancer (CRPC) Receiving First-line Docetaxel Chemotherapy

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Trial Acronym

CEPTAS

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URL of the Trial

[---]*

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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.

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Organizational Data

  •   DRKS00004093
  •   2012/11/15
  •   2010/08/17
  •   yes
  •   [---]*
  •   [---]*
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Secondary IDs

  •   2010-018370-21 
  •   NCT01206036  (ClinicalTrials.gov)
  •   C-II-007  (Central European Society for Anticancer Drug Research)
  •   2010-018370-21 
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Health Condition or Problem studied

  •   Prostatic Neoplasms
  •   C61 -  Malignant neoplasm of prostate
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Interventions/Observational Groups

  •   Drug: Docetaxel
  •   Drug: Temsirolimus
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Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   [---]*
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Primary Outcome

- recommended dose; time frame: 10 months; 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; 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.

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Secondary Outcome

- safety as defined as occurence of treatment related adverse events; time frame: 10 months; 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; 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; 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; 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; 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; Phase II Part: Evaluation of toxicity using CTCAE v4.0
- PSA; time frame: 24 months; 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; Phase II Part: Quality of life using the EORTC questionnaire
- overall survival; time frame: 24 months; 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; Phase II Part: Frequency of medication for pain

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
  •  
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Recruitment

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  •   2010/07/31
  •   18
  •   Multicenter trial
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Inclusion Criteria

  •   Male
  •   18   Years
  •   no maximum age
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Additional Inclusion 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.


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.


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.


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Exclusion Criteria

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.

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.

Exclusion Criteria Phase II Part, Maintenance Period:

- Disease Progression in the first 8 cycles (up to 26 weeks).

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Addresses

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    • Central European Society for Anticancer Drug Research
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    • Tumor-und Brustzentrum ZeTuP, St. Gallen, Switzerland
    • Rudolf Morant, MD 
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    • Tumor-und Brustzentrum ZeTuP, St. Gallen, Switzerland
    • Rudolf Morant, MD 
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    •   [---]*
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting complete, follow-up continuing
  •   [---]*
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   7
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.