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

Prostatic Neoplasms Clinical Trial

— CEPTAS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01206036
• Other study ID #: C-II-007
• Secondary ID: 2010-018370-21
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 17, 2010
• Last updated: January 26, 2016
• Start date: July 2010
• Est. completion date: October 2015

Study information

• Verified date: January 2016
• Source: Central European Society for Anticancer Drug Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Germany	CESAR Study Center	Essen
Germany	CESAR Study Center	Freiburg

Sponsors (1)

Lead Sponsor	Collaborator
Central European Society for Anticancer Drug Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recommended dose	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.	10 months	Yes
Primary	disease progression-free survival	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.	24 months	Yes
Secondary	safety as defined as occurence of treatment related adverse events	Phase I Part: Secondary endpoint is the collection of safety data on the dose levels used in this part.	10 months	Yes
Secondary	overall response	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.	24 months	No
Secondary	1-year Disease-Progression Free Survival Rate	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.	24 months	No
Secondary	DPFS time	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.	24 months	No
Secondary	TTP-PSA	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)†"	24 months	No
Secondary	toxicity based on treatment-related toxicities using CTCAE v4.0	Phase II Part: Evaluation of toxicity using CTCAE v4.0	24 months	Yes
Secondary	PSA	Phase II Part: Proportion of patients with drop of PSA of > 30% in the evaluation period compared to baseline compared to baseline.	24 months	No
Secondary	quality of life	Phase II Part: Quality of life using the EORTC questionnaire	24 months	No
Secondary	overall survival	Phase II Part: overall survival (OS) measured from randomization until death or lost to follow up (censored survival time)	24 months	No
Secondary	Frequency of medication for pain	Phase II Part: Frequency of medication for pain	24 months	No

External Links

•   web page of CESAR (Central European Society for Anticancer Drug Research-EEIG)