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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Male
Prostate Cancer

Thank you

Trial Information

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


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.

- 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
chest, abdomen, and pelvis to check the status of the disease.

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 128 will be enrolled at MD
Anderson.


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) Any of the following
metastatic presentations: exclusive visceral metastases, radiographically predominant
lytic bone metastases identified by plain X-ray or CT scan, bulky (>5 cm in longest
dimension) lymphadenopathy or high-grade (gleason >8) tumor mass in the
prostate/pelvis. b) Low PSA ( ablation or at symptomatic progression in the castrate-setting) plus high volume
(>/=20) bone metastases. c) Elevated serum LDH (>/= 2 x ULN) or elevated serum CEA
>/= 2 x ULN) in the absence of other etiologies. d) Short interval ( 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 >/= 2 cm in diameter.

5. Patients may have received prior treatment with androgen ablative therapies (such as
bicalutamide, ketoconazole, DES, abiraterone) and/or "targeted" therapies (such as
tyrosine kinase inhibitors) but these therapies must be discontinued >/= 2 weeks
before initiation of study treatment. 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.

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 4 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 ("docetaxel refractory disease").; Non-responders are eligible even if they have
received <225mg/m^2 of docetaxel

10. If present, peripheral neuropathy must be
11. The following pretreatment laboratory data within 14 days before registration: a)
Absolute neutrophil count (ANC) >/= 1,500/ml ; b) Platelets >/= 100,000/ml ; c) Total
bilirubin due to Gilbert's syndrome ; d) SGPT, (ALT) AND/OR SGOT (AST) patient has liver metastases, >/= 30 ml/min. using the Cockroft-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
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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS)

Outcome Description:

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.

Outcome Time Frame:

42 days

Safety Issue:

Yes

Principal Investigator

Paul Corn, MD,PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2011-0727

NCT ID:

NCT01505868

Start Date:

July 2012

Completion Date:

Related Keywords:

  • Prostate Cancer
  • Prostate Cancer
  • Metastatic Castration-Resistant Prostate Cancer
  • mCRPC
  • Prior treatment with docetaxel
  • Cabazitaxel
  • Jevtana
  • Carboplatin
  • Paraplatin
  • Prednisone
  • Prostatic Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030