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

Sponsor

Rahul Aggarwal (Other)

Overall Status

Completed

CT.gov ID

NCT01594918

Collaborator

Sanofi (Industry)

Enrollment

Locations

Arm

60.7

Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: Cabazitaxel Drug: Mitoxantrone Drug: Prednisone Drug: Pegfilgrastim	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Cabazitaxel, Mitoxantrone, and Prednisone (CAMP) for Patients With Metastatic Castration-Resistant Prostate Cancer and no Prior Chemotherapy

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Jun 23, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cabazitaxel, Mitoxantrone, Prednisone	Drug: Cabazitaxel 25 mg/m2 or 20 mg/m2, IV, once every 21 days Other Names: Jevtana® XRP6258 RPR116258 Drug: Mitoxantrone 4 mg/m2, 6 mg/m2, 8 mg/m2, 10 mg/m2, or 12 mg/m2, IV, once every 21 days Other Names: Novantrone Drug: Prednisone 5 mg PO BID Drug: Pegfilgrastim 6 mg, SC, once every 21 days Other Names: Neulasta

Arm

Intervention/Treatment

Experimental: Cabazitaxel, Mitoxantrone, Prednisone

Drug: Cabazitaxel

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

Other Names:

Jevtana®

XRP6258

RPR116258

Drug: Mitoxantrone

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

Other Names:

Novantrone

Drug: Prednisone

5 mg PO BID

Drug: Pegfilgrastim

6 mg, SC, once every 21 days

Other Names:

Neulasta

Outcome Measures

Primary Outcome Measures

Determination of the maximum tolerated dose (MTD) of the combination of cabazitaxel and mitoxantrone/prednisone as chemotherapy for patients with metastatic CRPC who have not received prior chemotherapy for metastatic disease. [Participants will be followed for the duration of treatment, an expected average of 4 months.]

Secondary Outcome Measures

Dose Limiting Toxicity (DLT) [Participants will have AE/Toxicity evaluations every 21 days. Average study participation is approximately 4 months.]
Number of Grade 3 or greater non-hematologic toxicity recorded.
Reduction in Prostate Specific Antigen (PSA), of the combination of cabazitaxel and mitoxantrone/prednisone in patients with metastatic CRPC who have not received prior chemotherapy for metastatic disease. [Participants will have PSA assessments every 21 days. Average study participation is approximately 4 months.]
Efficacy of drug combination including objective response rate and duration of response [Participants will be followed for the duration of treatment, an expected average of 4 months.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the prostate.
Progressive metastatic prostate cancer (positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or LHRH agonist therapy).
Patients may have either non-measurable disease OR measurable disease
All patients must have a PSA ≥ 2 ng/mL.
Progressive disease based on any one of the following:
transaxial imaging
a rise in PSA
radionuclide bone scan

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

For patients with measurable disease, progression will be defined by the RECIST criteria.
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.
Radionuclide bone scan: new metastatic lesions
Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy.
ECOG Performance Status 0 -2.
Required Laboratory values:
Creatinine < 1.5 x upper limits of normal (ULN). If Cr. > 1.5 x ULN, then calculated creatinine clearance > 40cc/min.
ALT and AST within normal limits
Absolute neutrophil count > 2,000/mm3
Platelets > 100,000/ mm3
Hemoglobin > 8.0 gm/dL
Total bilirubin within normal limits
Ejection fraction by MUGA scan or echocardiogram ≥ lower limit of institutional normal.
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.
No other systemic therapies for prostate cancer within 28 days prior to initiation of this protocol.
Prior radiation therapy completed ≥ 4 weeks prior to enrollment.
No history of radiopharmaceuticals (strontium, samarium) for prostate cancer treatment.
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.
Life expectancy > 12 weeks.
Age ≥ 18 years
Inclusion of Minorities: Men and members of all ethnic groups are eligible for this trial.

Exclusion Criteria:

Patients with significant cardiovascular disease including congestive heart failure (NYHA class III or IV), active angina pectoris or myocardial infarction within 6 months.
Patients with serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
Patients with psychiatric illness/social situations that would limit compliance with study requirements.
Patients with pre-existing neuropathy greater than CTCAE Grade 1 (motor or sensory).
Patients with known prior severe hypersensitivity reactions to cabazitaxel or other agents containing polysorbate 80.
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.
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.]
Concurrent use of moderate to strong CYP3A4 inhibitors is not allowed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
3	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232