Treatment of Metastatic Castrate Resistant Prostate Cancer Patients According to Circulating Tumor Cells Kinetic

NCT03101046 | Completed Phase 2 DMC

• 2 other identifiers: GETUG-AFU-28 - UC-0160/16132016-002429-12
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

This study compares the biological activity of cabazitaxel (6 cycles) to that of docetaxel (6 cycles) in metastatic castrate-resistant prostate cancer (mCRPC) patients with docetaxel resistant mCRPC defined as ≥5 circulating tumor cells (CTCs) / 7.5 mL after 2 cycles of docetaxel. Patients with docetaxel resistant metastatic castration-resistant prostate cancer (mCRPC) based on circulating tumor cell (CTC) enumeration (patients with ≥5 CTCs / 7.5 mL before docetaxel chemotherapy and after 2 cycles of docetaxel) will receive either 6 additional cycles of docetaxel or 6 additional cycles of cabazitaxel after randomisation. A cohort of patients with docetaxel sensitive metastatic castration-resistant prostate cancer (mCRPC) based on circulating tumor cell (CTC) enumeration (patients ≥5 CTCs / 7.5 mL before docetaxel chemotherapy and \<5 CTCs / 7.5 mL after 2 cycles of docetaxel) will receive 6 additional cycles of docetaxel.

Conditions

Prostate Carcinoma; Castration-resistant Prostate Cancer; Circulating Tumor Cells; Chemotherapy

Keywords

Docetaxel; Cabazitaxel

Outcome Measures

Primary Outcomes (1)

• Biological activity of chemotherapy

  Biological activity of chemotherapy as defined as \< 5 CTCs per 7.5 ml at the end of chemotherapy with docetaxel or cabazitaxel.

  18 weeks after randomisation

Study Arms (2)

Group1: Arm A (standard arm) + Arm B (experimental arm)

OTHER

Arm A: Patients with docetaxel resistant mCRPC (defined as having ≥5 CTCs / 7.5 mL) will receive up to 8 additional cycles of docetaxel (75 mg/m² every 3 weeks) after randomization. Arm B: Patients with docetaxel resistant mCRPC (defined as having ≥5 CTCs / 7.5 mL) will receive up to 10 cycles of cabazitaxel (20 mg/m² every 3 weeks) after randomization.

Drug: Cabazitaxel; Drug: Docetaxel

Group 2: Cohort

OTHER

Patients with docetaxel sensitive mCRPC (defined as having \<5 CTCs / 7.5 mL) will receive up to 8 additional cycles of docetaxel (75 mg/m² every 3 weeks)

Drug: Docetaxel

Interventions

Cabazitaxel DRUG

Experimental treatment arm: patients will be treated with intravenous cabazitaxel 20 mg/m² every 3 weeks up to 10 cycles.

Also known as: JEVTANA

Group1: Arm A (standard arm) + Arm B (experimental arm)

Docetaxel DRUG

standard treatment arm and cohort: Docetaxel is administered at the dose of 75 mg/m² over 1 hour every 3 weeks for 6 cycles (D1=D22).

Group 2: Cohort; Group1: Arm A (standard arm) + Arm B (experimental arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed prior any study-related procedures
• Adult men ≥18 years
• Histologically confirmed prostate adenocarcinoma
• Metastatic disease as evidenced by imaging (bone scan, CT-scan, MRI and/or PET-choline).
• Documented progressive disease while receiving continuous hormonal treatment with luteinizing hormone-releasing hormone (LH-RH) agonist or antagonist or after surgical castration (at least one visceral or soft tissue metastatic lesion, including a new lesion). Patient with non-measurable disease must have documented rising prostate-specific antigen (PSA) levels or appearance of new lesion
• Effective castration assessed by testosterone levels ≤50 ng/dL
• Patients with a Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Patients affiliated to social security scheme

You may not qualify if:

• Prior chemotherapy for metastatic prostate cancer except estramustine \<1 year from the end of adjuvant and/or neoadjuvant chemotherapy for localized disease \<1 year from the end of chemotherapy for de novo metastatic prostate cancer
• Prior isotope therapy, whole pelvic radiotherapy or radiotherapy to \>30% of bone marrow
• Less than 1 month elapsed from prior treatment with radiotherapy, surgery and less than 2 weeks from any previous hormonal treatment except for LH-RH agonists/antagonists (which are to be continued). Patients may be treated with bisphosphonates prior to study entry which should be pursued,
• History of brain metastases, uncontrolled spinal cord compression, carcinomatous meningitis or new evidence of brain or leptomeningeal disease
• Patient with any of the following abnormal laboratory tests: hemoglobin \<10 g/dL, absolute neutrophil count \<1.5 x 10⁹/L, platelets \<100 x 10⁹/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN), total bilirubin \>1.0 ULN, creatinine clearance \<40 ml/mn (MDRD)
• History of hypersensitivity to polysorbate 80 or docetaxel
• Contraindication to the use of corticosteroids
• Peripheral neuropathy grade ≥2 according to NCI CTCAE v4.0
• Ventricular ejection fraction \<50% (echography or scintigraphy)
• Any of the following within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack
• Any of the following within 3 months prior to study entry: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, inflammatory bowel disease, pulmonary embolism or other uncontrolled thromboembolic event
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• Planned vaccination with a live or live-attenuated vaccines
• Participation in another clinical trial and any treatment with any investigational drug within 30 days prior to randomization
• Any illness or problem including geographic, psychiatric or psychological which is incompatible with being monitored during the trial

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• Institut du Cancer de Montpellier - Val d'Aurelle: collaborator
• Institut Bergonié: collaborator

Study Sites (5)

ICO-Site Paul Papin

Angers, 49055 cedex 02, France

Location

CHD Vendée

La Roche-sur-Yon, 85925 Cedex 9, France

Location

Centre Léon Berard

Lyon, 69008, France

Location

Stéphane CULINE

Paris, 75475, France

Location

ICO-Site René Gauducheau

Saint-Herblain, 44805, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplastic Cells, Circulating

Interventions

cabazitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Stéphane CULINE

  Hôpital Saint Louis Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: April 4, 2017
• Study Start: November 15, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 10, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)