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Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01505868
First received: December 30, 2011
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

This clinical research study is made up of 2 groups and 2 phases.

The goal of Phase 1 of this study is to learn the highest tolerated dose of the combination of cabazitaxel, carboplatin, and prednisone that can be given to patients with metastatic CRPC.

The goal of Phase 2 of this study is to learn if adding cabazitaxel to the combination of carboplatin and prednisone affects how the disease is controlled in patients with metastatic CRPC.

In both of these phases, the drug combinations will be compared to cabazitaxel alone.

The safety of the drug combinations will be studied in both phases and groups.

Cabazitaxel and carboplatin are both designed to interfere with the growth of cancer cells by stopping cell division.

Prednisone is a corticosteroid that is similar to a natural hormone made by your body. It is often given in combination with other chemotherapy to treat cancer.


Condition Intervention Phase
Prostate Cancer
Drug: Cabazitaxel
Drug: Prednisone
Drug: Carboplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: An Open Label Phase I/II Study of Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
    Evaluation of measurable disease response will follow the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines. Complete Response: The disappearance of all target lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease: At least a 20% increase in the sum of the longest diameter of target lesions. Stable Disease: Insufficient shrinkage to qualify for partial response, or insufficient increase to qualify for progressive disease.


Estimated Enrollment: 178
Study Start Date: July 2012
Estimated Primary Completion Date: July 2029 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel + Prednisone
Starting Dose: Cabazitaxel 25 mg/m² intravenously on Day 1 of each 3 week cycle, plus Prednisone 5 mg by mouth twice daily.
Drug: Cabazitaxel

25 mg/m² intravenously on Day 1 of each 3 week cycle.

Phase I Starting Dose: 20 mg/m2 intravenously on Day 1 of each 3 week cycle.

Phase II Starting Dose: Maximum Tolerated Dose (MTD) from Phase I.

Other Name: Jevtana
Drug: Prednisone
5 mg by mouth twice a day on day 1 of a 3 week cycle.
Experimental: Cabazitaxel + Carboplatin + Prednisone

Phase I Starting Dose: Cabazitaxel 20-25 mg/m² + Carboplatin AUC 3-4 intravenously on Day 1 of each 3 week cycle, plus Prednisone 5 mg by mouth twice a day.

Phase II Starting Dose: Maximum Tolerated Dose (MTD) from Phase I.

Drug: Cabazitaxel

25 mg/m² intravenously on Day 1 of each 3 week cycle.

Phase I Starting Dose: 20 mg/m2 intravenously on Day 1 of each 3 week cycle.

Phase II Starting Dose: Maximum Tolerated Dose (MTD) from Phase I.

Other Name: Jevtana
Drug: Prednisone
5 mg by mouth twice a day on day 1 of a 3 week cycle.
Drug: Carboplatin

Phase I Starting Dose: AUC 3 intravenously on Day 1 of each 3 week cycle.

Phase II Starting Dose: Maximum Tolerated Dose (MTD) from Phase I.

Other Name: Paraplatin

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Histologic evidence of prostate adenocarcinoma.
  2. In addition to patients with adenocarcinoma, patients with "anaplastic" features are also eligible as defined by at least one of the following: a)Histologic evidence of small cell prostate cancer (patients with small cell carcinoma on histology are not required to demonstrate castration-resistant progression); b) Any of the following metastatic presentations: (i) exclusive visceral metastases; (ii) radiographically predominant lytic bone metastases identified by plain X-ray or CT scan; (iii) bulky (>/=5 cm in longest dimension) lymphadenopathy (iv) Bulky (>/=5cm) tumor mass in the prostate/pelvis (v) Low PSA (</= 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>/=20) bone metastases; (vi) Elevated serum LDH (>/= 2 x ULN) or elevated serum CEA (>/= 2 x ULN) in the absence of other etiologies; (vii) Short interval (</= 180 days) to castrate-resistant progression following initiation of hormonal therapy
  3. Castration-resistant prostate cancer. Patients must have surgical or ongoing chemical castration (with LHRH agonists or LHRH antagonists), with a baseline testosterone level <50ng/dL
  4. Metastatic disease. Patients must have evidence for metastatic prostate cancer by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). If lymph node, visceral and/or soft-tissue metastases are the only evidence of metastasis, at least one lesion must be >/= 1.5 cm in diameter.
  5. Patients may have received prior treatment with androgen ablative therapies (such as bicalutamide, ketoconazole, DES, abiraterone, Xtandi, ARN-509) and/or "targeted" therapies (such as tyrosine kinase inhibitors). Androgen ablative therapies must be discontinued >/=3 days prior to initiation of study treatment with the exception of abiraterone and/or enzalutamide, which may be continued during study treatment per the practice preference of the treating physician. Patients who are predicted to benefit from an antiandrogen withdrawal response should be tested for this possibility before being considered for eligibility to this study. Targeted therapies must be discontinued >/= 2 weeks before initiation of study treatment.
  6. Both chemotherapy-naïve and patients previously treated with chemotherapy are eligible. Chemotherapy pretreated patients may have received a maximum of two prior systemic cytotoxic chemotherapies completed at least 3 weeks prior to initiation of study treatment.
  7. Patients must have documented evidence of progressive disease as defined by any of the following: a) PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >/= 2.0 ng/mL; b) New or increasing non-bone disease (RECIST); c) Positive bone scan with 2 or more new lesions (PCWG2).
  8. For purposes of stratification, patients will be categorized as "responders" or "non-responders" based on their response to prior docetaxel-based therapy. a) Responders will have demonstrated objective responses to first-line docetaxel as determined by any of the following: 1.Decrease in PSA level >/= 50% from baseline, maintained for >/= 6 weeks 2. Partial or complete response in lymph nodes and soft tissue metastases by RECIST; Responders must have received >/= 225mg/m^2 (~ 3 cycles) of docetaxel.
  9. #8 Continued) b) Patients not meeting response criteria above will be considered as non-responders. We anticipate 2 general categories of non-responders based on the following disease phenotypes: 1. Progressive disease on therapy without any objective evidence of response ("primary-resistant disease") 2.Progressive disease on therapy with prior objective evidence of response, but response duration is </= 6 weeks ("docetaxel refractory disease").; Non-responders are eligible even if they have received <225mg/m^2 of docetaxel
  10. If present, peripheral neuropathy must be </= grade 2
  11. The following pretreatment laboratory data within 14 days before registration: a) Absolute neutrophil count (ANC) >/= 1,500/ml (unless due to bone marrow infiltration by tumor in which case ANC >/=500/ml are allowed) ; b) Platelets >/= 100,000/ml (unless due to bone marrow infiltration by tumor in which case >/=50,000/ml are allowed); c) Total bilirubin </= Upper Limit of Normal with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome or if the patient has liver metastases and/or acute tumor-associated illness </= 4x ULN.; d) SGPT, (ALT) AND/OR SGOT (AST) </= 1.5 x the ULN or if patient has liver metastases and/or acute tumor-associated illness, </= 4x ULN.; e) Patient has creatinine clearance >/= 30 ml/min. using the Cockcroft-Gault equation.
  12. Men whose partner is a woman of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
  13. Patient or his legally authorized representative must provide written informed consent.
  14. Age >/= 18
  15. ECOG performance status </= 2

Exclusion Criteria:

  1. Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose
  2. Samarium-153 within 28 days of registration, or Strontium-89 within 12 weeks (84 days) of registration. Patients who have received 2 or more doses of bone-seeking radioisotopes are not eligible.
  3. Current treatment on another therapeutic clinical trial.
  4. Prior treatment with cabazitaxel and/or carboplatin
  5. Impending complication from bone metastases (fracture and/or cord compression). Properly treated or stabilized fractures and/or cord compression is allowed.
  6. Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis) requiring medical intervention. Properly treated urinary obstruction is allowed.
  7. Patient has an uncontrolled intercurrent illness (e.g., uncontrolled diabetes, uncontrolled hypertension).
  8. Patient has another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the patient's ability to provide informed consent or with the completion of treatment according to this protocol.
  9. Patients with a history of severe hypersensitivity reaction to JEVTANA® (cabazitaxel) or other drugs formulated with polysorbate 80.
  10. Patients with an active second malignancy that could, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this 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: NCT01505868

Contacts
Contact: Paul Corn, MD, PHD 713-792-2830

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute/ Wayne State University Recruiting
Detroit, Michigan, United States, 48201
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Sanofi
Investigators
Principal Investigator: Paul Corn, MD,PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01505868     History of Changes
Other Study ID Numbers: 2011-0727, NCI-2012-00059
Study First Received: December 30, 2011
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
mCRPC
Prior treatment with docetaxel
Cabazitaxel
Jevtana
Carboplatin
Paraplatin
Prednisone

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

ClinicalTrials.gov processed this record on November 24, 2014