Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (TAXYNERGY)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01718353
First received: October 29, 2012
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

Primary Objectives: - To explore the benefit of an early switch from docetaxel/prednisone to cabazitaxel/ prednisone in men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) who do not achieve ≥30% prostate-specific antigen (PSA) decline from baseline by cycle 4 with the initial docetaxel treatment. - To evaluate the circulating tumor cells (CTCs) with clinical response/resistance to docetaxel or cabazitaxel treatment Secondary Objectives: - To assess efficacy and safety of the two treatment strategies, switch from cabazitaxel/prednisone to docetaxel/prednisone and docetaxel/prednisone to cabazitaxel/prednisone. - To evaluate efficacy in patients receiving initial taxane treatment before the switch and efficacy under the alternate taxane after the switch within each initial treatment group.


Condition Intervention Phase
Prostate Cancer Metastatic
Drug: CABAZITAXEL (XRP6258)
Drug: DOCETAXEL (XRP6976)
Drug: prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial to Evaluate Benefit of Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers and Mechanisms of Taxane Resistance in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Not Received Prior Chemotherapy

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • PSA response rate [ Time Frame: Every 3 weeks, up to max 5 years ] [ Designated as safety issue: No ]
  • Circulating tumor cells (CTCs) with response to docetaxel or cabazitaxel treatment [ Time Frame: Up to max 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: up to max 5 years ] [ Designated as safety issue: No ]
  • PSA progression-free survival rate [ Time Frame: up to max 5 years ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: up to max 5 years ] [ Designated as safety issue: No ]
  • Radiographic progression-free survival (rPFS) rate [ Time Frame: up to max 5 years ] [ Designated as safety issue: No ]
  • Clinical progression-free survival (cPFS) [ Time Frame: up to max 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to max 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel plus prednisone
docetaxel 75mg/m2 will be administered intravenously every 3 weeks, plus prednisone 10 mg orally given daily. Patients who do achieve ≥30% PSA reduction from baseline by cycle 4, will continue with docetaxel until progression, death, unacceptable toxicity or patient's refusal of further study treatment. Patients who do not achieve ≥30% PSA reduction from baseline by cycle 4 will switch chemotherapy to receive cabazitaxel plus prednisone
Drug: DOCETAXEL (XRP6976)
Pharmaceutical form: solution Route of administration: intravenous
Drug: prednisone
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cabazitaxel plus prednisone
cabazitaxel 25mg/m2 will be administered intravenously every 3 weeks, plus prednisone 10 mg orally given daily. Patients who do achieve ≥30% PSA reduction from baseline by cycle 4, will continue with cabazitaxel until progression, death, unacceptable toxicity or patient's refusal of further study treatment. Patients who do not achieve ≥30% PSA reduction from baseline by cycle 4 will switch chemotherapy to receive docetaxel plus prednisone
Drug: CABAZITAXEL (XRP6258)
Pharmaceutical form: solution Route of administration: intravenous
Drug: prednisone
Pharmaceutical form: tablet Route of administration: oral

Detailed Description:

Patients will be treated until progressive disease, unacceptable toxicity, death or patient's refusal of further study treatment. All patients will be followed until death or the study cutoff date, whichever comes first. Study cut-off will be 6 months after the last patient last treatment. Patients alive at the cut-off date will be followed for overall survival. Collection of survival data after the cut-off date will be done every year for a maximum of 3 years.

  Eligibility

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

Inclusion criteria :

  • Histologically- or cytologically-confirmed prostate adenocarcinoma with documented distant metastases (M1 disease)
  • Progressive disease while receiving hormonal therapy or after surgical castration
  • Effective castration (serum testosterone levels ≤50 ng/dL) by orchiectomy and/or luteinizing hormone releasing hormone agonists or antagonist with or without anti-androgens.

Exclusion criteria:

  • Prior chemotherapy for prostate cancer, except estramustine and adjuvant/neoadjuvant treatment completed >3 years ago. Prior treatment with sipuleucel-T immunotherapy is allowed at the condition patient did not received prior chemotherapy.
  • Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of random allocation.
  • Prior beta isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
  • Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03) at the time of random allocation.
  • Less than 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status >2.
  • History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
  • Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa and pT1) bladder cancer are allowed, as well as any other cancer for which chemotherapy has been completed ≥3 years ago and from which the patient has been disease-free for ≥3 years.
  • Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to random allocation.
  • Any of the following within 6 months prior to study enrollment: 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 random allocation: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
  • Acquired immunodeficiency syndrome (AIDS)-related illnesses or known HIV disease requiring antiretroviral treatment.
  • Any severe acute or chronic medical condition which could impair the ability of the patient to participate in to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures.
  • Concomitant treatment with biphosphonates or denosumab except if the dose has been stable for 12 weeks prior to enrollment
  • Absence of signed and dated Institutional Review Board (IRB)-approved patient informed consent prior to enrollment into the study.
  • Patients with reproductive potential who do not agree to use an accepted and effective method of contraception during the study treatment period. The definition of "effective method of contraception" will be based on the investigator's judgment.
  • History of hypersensitivity to docetaxel or polysorbate 80.
  • Inadequate organ and bone marrow function
  • Contraindications to the use of corticosteroid treatment
  • Symptomatic peripheral neuropathy grade >2 (NCI CTCAE v.4.03).
  • Treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a two-week wash-out period is necessary for patients who are already on these treatments)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718353

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

  Show 25 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01718353     History of Changes
Other Study ID Numbers: CABAZL06056, U1111-1130-9893
Study First Received: October 29, 2012
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Docetaxel
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 28, 2014