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

This study is currently recruiting participants.
Verified December 2013 by University of California, San Francisco
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Eric Small, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01594918
First received: May 7, 2012
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Metastatic Castration-resistant Prostate Cancer
Drug: Cabazitaxel
Drug: Mitoxantrone
Drug: Prednisone
Drug: Pegfilgrastim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

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. [ Time Frame: Participants will be followed for the duration of treatment, an expected average of 4 months. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: Participants will have AE/Toxicity evaluations every 21 days. Average study participation is approximately 4 months. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Participants will have PSA assessments every 21 days. Average study participation is approximately 4 months. ] [ Designated as safety issue: No ]
  • Efficacy of drug combination including objective response rate and duration of response [ Time Frame: Participants will be followed for the duration of treatment, an expected average of 4 months. ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: June 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Novantrone
Drug: Prednisone
5 mg PO BID
Drug: Pegfilgrastim
6 mg, SC, once every 21 days
Other Name: Neulasta

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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:

    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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01594918

Contacts
Contact: Eric Small, MD (415) 353-7095 smalle@medicine.ucsf.edu

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Office    507-538-7623      
Principal Investigator: Alan Bryce, MD         
United States, California
UCSF Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Paula Dutton    415-885-7871    walshp@medicine.ucsf.edu   
Principal Investigator: Eric Small, MD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Clinical Trials Information Program    800-811-8480      
Principal Investigator: Christina Derleth, MD         
Sponsors and Collaborators
Eric Small
Sanofi
Investigators
Study Chair: Eric Small, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Eric Small, Clinical Professor of Medicine and Urology, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01594918     History of Changes
Other Study ID Numbers: UCSF Protocol No. 11951
Study First Received: May 7, 2012
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
metastatic
CRPC
prostate
CAMP

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Mitoxantrone
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 16, 2014