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Cabazitaxel in mCRPC Patients With AR-V7 Positive CTCs (CARVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02621190
Recruitment Status : Withdrawn (no approval)
First Posted : December 3, 2015
Last Update Posted : August 17, 2016
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
M.P.J.K. Lolkema, Erasmus Medical Center

Brief Summary:
After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available. In retrospective studies, resistance has been described to two of the treatment options, enzalutamide and abiraterone, when a splice variant of the Androgen Receptor (AR-V7) is present on circulating tumor cells (CTCs). The investigators hypothesize that patients with AR-V7 positive CTCs do have a meaningful response to cabazitaxel.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: cabazitaxel Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Non-randomized Phase 2 Open-label Multicenter Study Determining the Response to Cabazitaxel in Metastatic Prostate Cancer (mCRPC) Patients With AR-V7 Positive Circulating Tumor Cells (CTCs): CARVE
Study Start Date : February 2016
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Cabazitaxel

Arm Intervention/treatment
No Intervention: A
patients without CTCs or AR-V7 negative CTCs are treated according to their physician's discretion
Experimental: B
patients with AR-V7 positive CTCs are treated with cabazitaxel 25mg/m2 q3w
Drug: cabazitaxel
25mg/m2 q3w
Other Name: Jevtana




Primary Outcome Measures :
  1. Prostate specific antigen (PSA) response rate [ Time Frame: 12 weeks after start of treatment ]
    PSA response rate is defined as a reduction of at least 50% from baseline during therapy, confirmed after ≥4 weeks by an additional PSA evaluation.


Secondary Outcome Measures :
  1. Circulating tumor cell (CTC) response rate [ Time Frame: 9 weeks after start of treatment ]
    CTC Response rate is defined as a decrease from ≥5 CTCs per 7.5 mL blood at baseline to <5 CTCs per 7.5 mL blood, as measured by the CellSearch system

  2. Prostate specific antigen (PSA) change from baseline [ Time Frame: 12 weeks after start of treatment ]
    • PSA change from baseline at 12 weeks defined as the percent change in PSA from baseline (rise or fall) at 12 weeks, according to PCWG2 criteria.

  3. Maximum Prostate specific antigen (PSA) decrease [ Time Frame: through study completion, an average of two years ]
    Maximum PSA decrease is defined according to PCWG2 criteria (30), i.e., the maximal change (rise or fall) at any time through study completion, illustrated by a waterfall plot

  4. Progression-free survival [ Time Frame: from date of treatment allocation until the date of first documented progression (see description) or date of death from any cause, whichever came first, assessed through study completion, up to 100 months ]

    Progression defined as:

    • At least 2 consecutive PSA rises over a reference value, with an interval of ≥ 1 week between each determination. PSA at screening visit should be ≥ 2.0 μg/l; the date of progression will be the first of the 2 consecutive dates.
    • Soft tissue disease progression defined by modified RECIST criteria (1.1) (baseline LN size must be ≥ 2.0 cm to be considered target or evaluable lesion).
    • Bone disease progression defined by the appearance of new lesions on a bone scan, confirmed on a second bone scan ≥ 6 weeks later. Ambiguous results should be confirmed by other imaging modalities (e.g., CT or MRI). The date of progression will be the first of the 2 consecutive dates.

  5. Overall survival [ Time Frame: time from treatment group allocation to death due to any cause, assessed through study completion, up to 100 months ]
  6. grade 3-4 adverse events and serious adverse events (SAEs) [ Time Frame: through study treatment until 30 days after end of treatment ]
  7. Cabazitaxel concentration in the blood (measured in ng/mL) [ Time Frame: during the first cycle of cabazitaxel, until 6 hours after end of cabazitaxel infusion ]
  8. Total systemic exposure to cabazitaxel (measured in mg/m2) [ Time Frame: through study treatment, an average of 10 cycles, i.e., 30 weeks of treatment ]
  9. AR-V7 mRNA expression as well as mRNA expression of other splice variants in CTCs indicated as absent (─) or present (+) on a per-patient basis [ Time Frame: at screening visit ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.

    • Continued androgen deprivation therapy either by LHRH agonists/antagonists or orchiectomy.
    • Serum testosterone <50 ng/mL (1.7 nmol/L) within 21 days before treatment group allocation.
    • Age ≥18 years
    • Disease progression during or after treatment with docetaxel. Disease progression for study entry is defined as one or more of the following criteria:

      • PSA progression defined by at least 2 consecutive PSA rises over a reference value, with an interval of ≥ 1 week between each determination. PSA at screening visit should be ≥ 2.0 μg/l.
      • Bone disease progression defined by the appearance of new lesions on a bone scan, confirmed on a second bone scan ≥ 6 weeks later.
      • Soft tissue disease progression defined by modified RECIST criteria 1.1 (baseline LN size must be ≥ 2.0 cm to be considered target or evaluable lesion) (15)
    • ECOG performance status 0-2 (appendix A)
    • Written informed consent according to ICH-GCP before study treatment and any study specific procedures

Exclusion Criteria:

  • Impossibility or unwillingness to take oral drugs

    • Geographical, psychological or other non-medical conditions interfering with follow-up
    • Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection)
    • Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.
    • Chemotherapy or immunotherapy (other than LHRH analogues) within the last 4 weeks before study inclusion.
    • Prior treatment with cabazitaxel
    • Successive treatment with both abiraterone and enzalutamide in the post-docetaxel setting
    • Radiotherapy to 40% or more of the bone marrow
    • Known hypersensitivity to corticosteroids
    • History of severe hypersensitivity reaction (≥grade 3) to docetaxel
    • History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
    • Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix C)
    • Concomitant vaccination with yellow fever vaccine
    • Abnormal liver functions consisting of any of the following (within 21 days before treatment group allocation):
    • Total bilirubin > 1.5 x ULN (except for patients with documented Gilbert's disease)
    • If total bilirubin > 1 x ULN or AST > 1.5 x ULN inclusion is permitted but cabazitaxel dose should be reduced 20mg/m2
    • Abnormal hematological blood counts consisting of any of the following (within 21 days before treatment group allocation):
    • Absolute neutrophil count < 1.5 x 109/L
    • Platelets < 100 x 109/L
    • Hemoglobin < 6.2 mmol/L

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02621190


Locations
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Netherlands
Erasmus MC Cancer Institute
Rotterdam, Netherlands, 3075 EA
Sponsors and Collaborators
Erasmus Medical Center
Sanofi
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Responsible Party: M.P.J.K. Lolkema, oncologist, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02621190    
Other Study ID Numbers: NL55865.078.15
First Posted: December 3, 2015    Key Record Dates
Last Update Posted: August 17, 2016
Last Verified: August 2016
Keywords provided by M.P.J.K. Lolkema, Erasmus Medical Center:
circulating tumor cells
predictive factor
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases