Phase I Cabazitaxel, Mitoxantrone, and Prednisone Metastatic Castration-Resistant Prostate Cancer

NCT ID: NCT01594918

Last Updated: 2017-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2017-06-23

Brief Summary

The purpose of this study is to test the safety of cabazitaxel, mitoxantrone, and prednisone (CAMP) in combination at different dose levels and to determine the highest dose that does not cause bad side effects. The investigators want to find out what effects, good and/or bad, CAMP has on patients and their metastatic castration-resistant prostate cancer.

Detailed Description

This is a Phase I, open label, dose-finding, multicenter clinical trial to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of cabazitaxel (25 mg/m2 IV q21 days) in combination with mitoxantrone (4-12 mg/m2 IV q21 days) and prednisone (5mg orally BID) in patients with metastatic CRPC who have not undergone prior chemotherapy for metastatic disease.

Up to five cohorts will be enrolled to determine the MTD and DLT profile of this combination. An accelerated titration design method is being used in order to minimize the number of patients exposed to subtherapeutic doses of mitoxantrone.

Conditions

Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabazitaxel, Mitoxantrone, Prednisone

Group Type: EXPERIMENTAL

Cabazitaxel

Intervention Type: DRUG

25 mg/m2 or 20 mg/m2, IV, once every 21 days

Mitoxantrone

Intervention Type: DRUG

4 mg/m2, 6 mg/m2, 8 mg/m2, 10 mg/m2, or 12 mg/m2, IV, once every 21 days

Prednisone

Intervention Type: DRUG

5 mg PO BID

Pegfilgrastim

Intervention Type: DRUG

6 mg, SC, once every 21 days

Interventions

Cabazitaxel

25 mg/m2 or 20 mg/m2, IV, once every 21 days

Intervention Type: DRUG

Mitoxantrone

4 mg/m2, 6 mg/m2, 8 mg/m2, 10 mg/m2, or 12 mg/m2, IV, once every 21 days

Intervention Type: DRUG

Prednisone

5 mg PO BID

Intervention Type: DRUG

Pegfilgrastim

6 mg, SC, once every 21 days

Intervention Type: DRUG

Other Intervention Names

Jevtana®; XRP6258; RPR116258; Novantrone; Neulasta

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed adenocarcinoma of the prostate.

2. Progressive metastatic prostate cancer (positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or LHRH agonist therapy).

3. Patients may have either non-measurable disease OR measurable disease

4. All patients must have a PSA ≥ 2 ng/mL.

5. Progressive disease based on any one of the following:

1. transaxial imaging

2. a rise in PSA

3. radionuclide bone scan

Patients whose sole manifestation of progression is an increase in disease-related symptoms are not eligible.

1. For patients with measurable disease, progression will be defined by the RECIST criteria.

2. For patients with non-measurable disease, a positive bone scan and elevated PSA will be required. PSA evidence for progressive prostate cancer during or after first-line chemotherapy consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than the screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression for the purposes of eligibility.

3. Radionuclide bone scan: new metastatic lesions

6. Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy.

7. ECOG Performance Status 0 -2.

8. Required Laboratory values:

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1. Creatinine < 1.5 x upper limits of normal (ULN). If Cr. > 1.5 x ULN, then calculated creatinine clearance > 40cc/min.

2. ALT and AST within normal limits

3. Absolute neutrophil count > 2,000/mm3

4. Platelets > 100,000/ mm3

5. Hemoglobin > 8.0 gm/dL

6. Total bilirubin within normal limits

9. Ejection fraction by MUGA scan or echocardiogram ≥ lower limit of institutional normal.

10. Patients receiving hormonal therapy (i.e. any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES) other than LHRH agonist/antagonist or a stable dose of corticosteroid from a prior chemotherapy regimen must discontinue the agent for at least 4 weeks prior to enrollment. Progressive disease must be documented after discontinuation of the hormonal therapy.

11. No other systemic therapies for prostate cancer within 28 days prior to initiation of this protocol.

12. Prior radiation therapy completed ≥ 4 weeks prior to enrollment.

13. No history of radiopharmaceuticals (strontium, samarium) for prostate cancer treatment.

14. Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy. Should a patient's sexual partner become pregnant or suspect she is pregnant while the patient is participating in this study, he should inform the treating physician immediately.

15. Life expectancy > 12 weeks.

16. Age ≥ 18 years

17. Inclusion of Minorities: Men and members of all ethnic groups are eligible for this trial.

Exclusion Criteria

1. Patients with significant cardiovascular disease including congestive heart failure (NYHA class III or IV), active angina pectoris or myocardial infarction within 6 months.

2. Patients with serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.

3. Patients with psychiatric illness/social situations that would limit compliance with study requirements.

4. Patients with pre-existing neuropathy greater than CTCAE Grade 1 (motor or sensory).

5. Patients with known prior severe hypersensitivity reactions to cabazitaxel or other agents containing polysorbate 80.

6. Patients with known active brain metastases are excluded because of their poor prognosis. Head CT is NOT routinely required prior to enrollment. Patients with treated, asymptomatic brain metastasis will be eligible for enrollment.

7. Patients with a "currently active" second malignancy other than non-melanoma skin cancer are excluded. [Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.]

8. Concurrent use of moderate to strong CYP3A4 inhibitors is not allowed.

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

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Rahul Aggarwal

OTHER

Sponsor Role: lead

Responsible Party

Rahul Aggarwal

Assistant Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rahul Aggarwal, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

Mayo Clinic

Scottsdale, Arizona, United States

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

UCSF Protocol No. 11951

Identifier Type: -

Identifier Source: org_study_id