A Study Looking at Novel Scheduling of Cabazitaxel for Patients With Metastatic Prostate Cancer - Full Text View

Purpose

Cabazitaxel has shown significant efficacy as second line chemotherapy after Docetaxel in men with metastatic castration resistant prostate cancer. This was demonstrated in the Tropic Study where Cabazitaxel showed survival superiority compared to mitoxantrone. Almost one in 4 patients treated with Cabazitaxel in this study required dose reductions or dose delays or stopped treatment due to toxicity. ConCab examines another scheduling for cabazitaxel to see if we can improve tolerability so that patients will receive a higher percentage of the treatment as planned.

Condition	Intervention	Phase
Metastatic Castration Resistant Prostate Cancer	Drug: Cabazitaxel Drug: weekly cabazitaxel	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized, Open Label, Multicenter, Phase II Trial Comparing The Conventional 3 Weekly Schedule Of Cabazitaxel With A Weekly Regimen In Patients With Metastatic Castration Resistant Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Cabazitaxel

U.S. FDA Resources

Further study details as provided by Karolinska University Hospital:

Primary Outcome Measures:

Relative cumulative dose of cabazitaxel at week 18 [ Time Frame: week 18 after start of treatment ] [ Designated as safety issue: Yes ]
The primary endpoint compares the cumulative dose of cabazitaxel that is received relative to the planned dose at 18 weeks of therapy. The cumulative dose of cabazitaxel in relation to the expected dose is a reflection of both tolerability and efficacy. Patients stopping treatment due to disease progression prior to week 18 will have lower relative cumulative doses as will patients with poor tolerability due to dose reductions and delays.

Secondary Outcome Measures:

Overall Survival [ Time Frame: when the last enrolled patient has completed 18 weeks of therapy or has stopped therapy at an earlier date ] [ Designated as safety issue: No ]
Overall survival is defined as the length of time from randomization to death from any cause
Progression free survival [ Time Frame: when the last enrolled patient has completed 18 weeks of therapy or has stopped therapy at an earlier date ] [ Designated as safety issue: No ]
Progression free survival is defined as the length of time from randomisation to the first documentation of one of the following: PSA progression or pain progression or death due to any cause or radiological disease progression
PSA Response [ Time Frame: when the last enrolled patient has completed 18 weeks of therapy or has stopped therapy at an earlier date ] [ Designated as safety issue: No ]
Only considered after 12 weeks of treatment. PSA response is defined as a 50% or greater decline in serum PSA from baseline given that baseline PSA is at least 10 ng/ml

Estimated Enrollment:	100
Study Start Date:	March 2012
Estimated Study Completion Date:	October 2015
Estimated Primary Completion Date:	June 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Standard Cabazitaxel Schedule Cabazitaxel 25 mg/m2 every three weeks	Drug: Cabazitaxel 25 mg/m2 every three weeks
Experimental: Weekly cabazitaxel schedule cabazitaxel 10 mg/m2 given weekly for 5 consecutive weeks of a six week cycle	Drug: weekly cabazitaxel 10 mg/m2 dag 1,8,15,22. Cycle length is 6 weeks

Detailed Description:

ConCab compares the standard treatment of cabazitaxel 25 mg/m2 every three weeks with an experimental scheduling of 10 mg/m2 for 5 consecutive weeks of a 6 week cycle. In both study arms the planned cumulative dose of cabazitaxel at week 18 is 150 mg/m2. Our study aims to evaluate differences in the total received dose in relation to the planned dose as a measure of which of the 2 treatment schedules is superior.

Eligibility

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

Criteria

Inclusion Criteria:¨

Histological confirmed prostate cancer
Macroscopic metastatic disease
Prior treatment with Docetaxel
Castration resistant disease defined as:Serum testosterone (< 0.5 ng/ml) and:
Increase in measurable disease (RECIST 1.1, see appendix 10) or
For non-measurable disease, the appearance of at least one new lesion on nuclear scintigraphy) or
A rising PSA from the previous reference value on 2 consecutive occasions at least one week apart
Written informed consent

Exclusion Criteria:

Less than 21 days since prior treatment with chemotherapy
Less than 14 days since radiotherapy or surgery to the start of cabazitaxel - Less than 4 weeks after stopping endocrine therapies including antiandrogen, abiraterone or other new agents.
Prior isotope therapy or radiotherapy to > 30% of bone marrow (whole pelvic radiotherapy is not an exclusion criteria)
Persistent adverse events from previous cancer therapies > grade 1 (CTCAE - Version 4.0) with the exception of alopecia. (With respect to peripheral neuropathy and nail changes grade 2 is acceptable)
ECOG performance status > 1
Known CNS malignancy
Within 6 months of randomization:
- myocardial infarction,
- unstable angina,
- angioplasty,
- bypass surgery,
- stroke,
- TIA, or
- congestive heart failure NYHA class III or IV
Within 3 months prior to randomization:
- treatment resistant peptic ulcer disease,
- infectious or inflammatory bowel disease,
- pulmonary embolism
- Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results
History of hypersensitivity to docetaxel or polysorbate 80
Inadequate organ and bone marrow function as evidenced by:
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count < 1.5 x 109/L,
- Platelet count < 100 x 109/L,
- AST/SGOT and/or ALT/SGPT > 1.5 x ULN;
- Total bilirubin > 1.0 x ULN,
- Serum creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance < 60 mL/min should be excluded (http://mdrd.com/ for on-line calculation)
Concurrent or planned treatment with potent inhibitors or inducers of cytochrome P450 3A4/5. A one week wash out period is necessary for patients who are already on these treatments.
Patients with reproductive potential not implementing accepted and effective method of contraception.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541007

Contacts

Contact: Jeffrey R Yachnin, MD, PhD	46-8-517-74345	jeffrey.yachnin@karolinska.se
Contact: Anders Ullén, MD, PhD	46-8-517-70000	anders.ullen@karolinska.se

Locations

Sweden
Deapartment of Oncology Karolinska University Hospital	Recruiting
Stockholm, Sweden, 171 76
Principal Investigator: Anders Ullén, MD, PhD

Sponsors and Collaborators

Jeffrey Yachnin M.D., PhD.

Sanofi

Investigators

Study Chair:

Jeffrey R Yachnin, MD, PhD

Karolinska University Hosptial

More Information

No publications provided

Responsible Party:	Jeffrey Yachnin M.D., PhD., Director Clinical Trials Unit, Karolinska University Hospital
ClinicalTrials.gov Identifier:	NCT01541007 History of Changes
Other Study ID Numbers:	2011-004178-27
Study First Received:	February 23, 2012
Last Updated:	March 5, 2012
Health Authority:	Sweden: Medical Products Agency

Keywords provided by Karolinska University Hospital:

Prostate Cancer
Metastatic
Castration Resistant

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site

Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on May 23, 2013

A Study Looking at Novel Scheduling of Cabazitaxel for Patients With Metastatic Prostate Cancer (ConCab)