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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Cabazitaxel; Drug: Mitoxantrone; Drug: Prednisone; Drug: Pegfilgrastim

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 Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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:

   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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity (DLT)	Number of Grade 3 or greater non-hematologic toxicity recorded.	Participants will have AE/Toxicity evaluations every 21 days. Average study participation is approximately 4 months.
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.

Collaborators and Investigators

• Sponsor: Rahul Aggarwal
• Collaborators: Sanofi
• Investigators: Study Chair: Rahul Aggarwal, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): June 23, 2017

Study Registration Dates

• First Submitted: May 7, 2012
• First Submitted That Met QC Criteria: May 7, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 20, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: metastatic; prostate; CRPC; CAMP
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Prednisone; Mitoxantrone
• Other Study ID Numbers: UCSF Protocol No. 11951