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)

NCT ID: NCT01718353

Last Updated: 2017-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2015-08-31

Brief Summary

Docetaxel and cabazitaxel are cancer chemotherapy agents of the taxane drug class. The purpose of this study is to explore the benefit, for treatment of metastatic castration-resistant prostate cancer (mCRPC), of a regimen in which participants begin treatment with either of these two taxane drugs (docetaxel or cabazitaxel, in combination with prednisone) and are switched to the other taxane drug if prostate-specific antigen (PSA) value does not decrease ≥30% after 4 cycles. As defined in study protocol amendment 3, efficacy results are summarized for all participants combined, irrespective of which agent (docetaxel or cabazitaxel) was administered initially, rather than separately for the two groups based on taxane administered initially. One of the primary outcome measures is percentage of participants with a ≥50% sustained decrease from baseline in PSA at any time during the trial. By providing an opportunity for patients to switch taxane based on early PSA response, there may be a difference in result for this measure versus result in a study where it was not possible to switch. The other primary outcome measures are change from baseline in circulating tumor cells (CTCs) biomarkers percent androgen receptor nuclear localization (%ARNL) and microtubule bundling (MTB).

Detailed Description

• Participants were treated until progressive disease, unacceptable toxicity, death, or participant's refusal of further study treatment. All participants were followed until death or the study cut-off date, whichever came first.
• Study cut-off was 1 month after the last participant last treatment.
• Participants alive at the cut-off date were not followed for overall survival.

Conditions

Prostate Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel + Prednisone (Treatment A)

Docetaxel 75 mg/m\^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.

Group Type: EXPERIMENTAL

DOCETAXEL (XRP6976)

Intervention Type: DRUG

Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Cabazitaxel + Prednisone (Treatment B)

Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.

Group Type: EXPERIMENTAL

CABAZITAXEL (XRP6258)

Intervention Type: DRUG

Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Interventions

DOCETAXEL (XRP6976)

Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Intervention Type: DRUG

CABAZITAXEL (XRP6258)

Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous

Intervention Type: DRUG

Prednisone

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

Taxotere®; Jevtana®

Eligibility 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 was allowed at the condition participant did not receive 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.
• 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 were allowed, as well as any other cancer for which chemotherapy had been completed ≥3 years ago and from which the participant had 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 participant to participate in to the study or interfere with interpretation of study results, or participant unable to comply with the study procedures.
• Concomitant treatment with biphosphonates or denosumab except if the dose had been stable for 4 weeks prior to enrollment.
• Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent prior to enrollment into the study.
• Participants with reproductive potential who did not agree to use an accepted and effective method of contraception during the study treatment period. The definition of "effective method of contraception" was 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 was necessary for participants who were already on these treatments).

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840003

Birmingham, Alabama, United States

Investigational Site Number 840102

Washington D.C., District of Columbia, United States

Investigational Site Number 840005

Indianapolis, Indiana, United States

Investigational Site Number 840025

Metairie, Louisiana, United States

Investigational Site Number 840002

Baltimore, Maryland, United States

Investigational Site Number 840007

Bethesda, Maryland, United States

Investigational Site Number 840017

Rockville, Maryland, United States

Investigational Site Number 840010

Cherry Hill, New Jersey, United States

Investigational Site Number 840015

East Orange, New Jersey, United States

Investigational Site Number 840001

New York, New York, United States

Investigational Site Number 840013

New York, New York, United States

Investigational Site Number 840009

Charleston, South Carolina, United States

Investigational Site Number 840012

Seattle, Washington, United States

Investigational Site Number 840004

Madison, Wisconsin, United States

Investigational Site Number 124001

Edmonton, Alberta, Canada

Investigational Site Number 124004

Montreal, Quebec, Canada

Investigational Site Number 124002

Montreal, Quebec, Canada

Investigational Site Number 124006

Québec, Quebec, Canada

Investigational Site Number 124005

Sherbrooke, Quebec, Canada

Countries

United States; Canada

References

Tagawa ST, Antonarakis ES, Gjyrezi A, Galletti G, Kim S, Worroll D, Stewart J, Zaher A, Szatrowski TP, Ballman KV, Kita K, Tasaki S, Bai Y, Portella L, Kirby BJ, Saad F, Eisenberger MA, Nanus DM, Giannakakou P. Expression of AR-V7 and ARv567es in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY. Clin Cancer Res. 2019 Mar 15;25(6):1880-1888. doi: 10.1158/1078-0432.CCR-18-0320. Epub 2018 Oct 9.

Reference Type: DERIVED

PMID: 30301829 (View on PubMed)

Antonarakis ES, Tagawa ST, Galletti G, Worroll D, Ballman K, Vanhuyse M, Sonpavde G, North S, Albany C, Tsao CK, Stewart J, Zaher A, Szatrowski T, Zhou W, Gjyrezi A, Tasaki S, Portella L, Bai Y, Lannin TB, Suri S, Gruber CN, Pratt ED, Kirby BJ, Eisenberger MA, Nanus DM, Saad F, Giannakakou P; TAXYNERGY Investigators. Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naive, Metastatic, Castration-Resistant Prostate Cancer. J Clin Oncol. 2017 Oct 1;35(28):3181-3188. doi: 10.1200/JCO.2017.72.4138. Epub 2017 Jun 20.

Reference Type: DERIVED

PMID: 28632486 (View on PubMed)

Other Identifiers

U1111-1130-9893

Identifier Type: OTHER

Identifier Source: secondary_id

CABAZL06056

Identifier Type: -

Identifier Source: org_study_id