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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: Cabazitaxel; Drug: weekly cabazitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 171 76
    • Deapartment of Oncology Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative cumulative dose of cabazitaxel at week 18	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.	week 18 after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as the length of time from randomization to death from any cause	when the last enrolled patient has completed 18 weeks of therapy or has stopped therapy at an earlier date
Progression free survival	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	when the last enrolled patient has completed 18 weeks of therapy or has stopped therapy at an earlier date
PSA Response	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	when the last enrolled patient has completed 18 weeks of therapy or has stopped therapy at an earlier date

Collaborators and Investigators

• Sponsor: Jeffrey Yachnin M.D., PhD.
• Collaborators: Sanofi
• Investigators: Study Chair: Jeffrey R Yachnin, MD, PhD, Karolinska University Hosptial

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: February 28, 2012
• First Posted (ESTIMATE): February 29, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 1, 2015
• Last Update Submitted That Met QC Criteria: October 30, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Prostate Cancer; Metastatic; Castration Resistant
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2011-004178-27