Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy
This trial is active, not recruiting.
|Treatments||cabazitaxel, prednisone, carboplatin|
|Phase||phase 1/phase 2|
|Sponsor||M.D. Anderson Cancer Center|
|Start date||July 2012|
|End date||July 2029|
|Trial size||178 participants|
|Trial identifier||NCT01505868, 2011-0727, NCI-2012-00059|
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.
|United States||No locations recruiting|
|Other Countries||No locations recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
|Masking||single blind (subject)|
Progression Free Survival (PFS)
time frame: 42 days
Male participants at least 18 years old.
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.
|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|
|Principal investigator||Paul Corn, MD,PHD|
|Description||Study Groups: If you are found to be eligible to take part in this study, you will be assigned to 1 of 2 treatment groups (depending on when you enroll). - If you are in Group 1, you will receive cabazitaxel plus prednisone. - If you are in Group 2, you will receive cabazitaxel in combination with carboplatin plus prednisone. The first 9-18 participants will be assigned to Group 2 and enrolled in the Phase I portion of the study. If you are enrolled in the Phase I portion, the combination dose of carboplatin and cabazitaxel you receive will depend on when you joined this study. The first group of participants will receive the lowest combination dose level. Each new group will receive a higher combination dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable combination dose of carboplatin and cabazitaxel is found. Once the highest tolerable combination dose is found, all patients enrolled after that will be randomly assigned (as in the flip of a coin) to a study group in Phase 2. You will have an equal chance of being assigned to each group. Your study doctor will tell you which phase and group you are in, and the dose level of the drugs you will receive. All participants will receive the same dose level of prednisone. Study Drug Administration: You will receive cabazitaxel by vein over about 60 minutes on Day 1 of each 21-day study cycle. If you receive carboplatin, you will also receive it by vein, after your cabazitaxel dose, over about 60 minutes on Day 1 of each cycle. You will take prednisone tablets by mouth twice a day (morning and evening), on Day 1 of each cycle. About 30 minutes before you receive the study drug(s), you will be given drugs (for example, the drug filgrastim) to help prevent side effects. Your doctor will describe these drugs to you in more detail, including how they are given and any side effects you may expect. Study Visits: On Day 1 of each cycle: - Your complete medical history will be recorded. - You will have a physical exam. - Your weight and vital signs will be recorded. - Your performance status will be recorded. - You will be asked about any side effects you may have experienced and about any drugs you may be taking. - Blood (about 3 teaspoons) and urine will be collected for routine tests. These tests can be done up to 7 days before this visit. On 1 day between Days 7 and 10 of Cycle 1, blood (about 3 teaspoons) will be drawn for routine tests. If the doctor thinks it is needed during any other cycle, this blood draw will be repeated. After every 2 cycles, you will have a bone scan and either a CT scan or MRI scan of your abdomen, and pelvis to check the status of the disease. If the study doctor thinks it is needed, you will also have a chest CT scan. If the study doctor thinks it is needed, you will also have blood drawn (about 3 teaspoons) for routine testing. Length of Treatment: You may receive the study drug(s) for up to 10 total cycles. You will be taken off study if intolerable side effects occur, if you are unable to follow study directions, or if the disease gets worse. Your participation on the study will be over once you have completed the end-of-dosing and follow-up visits. End-of-Dosing Visit: After you are no longer receiving the study drug(s), you will have an end-of-dosing visit. The following tests and procedures will be performed: - Your complete medical history will be recorded. - You will have a physical exam. - Your weight and vital signs will be recorded. - You will be asked about any side effects you may have experienced and about any drugs you may be taking. - Blood (about 3 tablespoons) and urine will be collected for routine tests. - You will have either a CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease. - If your doctor thinks it is needed, you will have a bone scan to check the status of the disease. Long-term Follow-up: After the end-of-dosing visit, the study staff will call you or review your medical record. If contacted by phone, you will be asked about how you are feeling and any side effects you may have had. Each follow-up call will take about 5 minutes. Follow-up will take place every 6 months after you stop taking the study drugs. This is an investigational study. Cabazitaxel, carboplatin, and prednisone are FDA approved and commercially available. The use of these drugs in combination for the treatment of prostate cancer is investigational. Up to 178 patients will be enrolled in this study. Up to 178 will be enrolled at MD Anderson.|
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