Cabazitaxel With Radiation and Hormone Therapy for Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01420250
First received: August 17, 2011
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

This is a single-center, open-label, non-randomized Phase I study of weekly Cabazitaxel with concurrent intensity modulated radiation therapy (IMRT) (A type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles.) and androgen deprivation therapy (Treatment to suppress or block the production or action of male hormones) in patients with locally advanced prostate cancer.

It is hoped that by adding Cabazitaxel to the standard IMRT, greater local disease control can be achieved and eventually the cure rate can be increased. After this study, the maximally tolerated dose of Cabazitaxel that could be used in combination with radiation can be found.

Men with locally advanced high risk prostate cancer represent a group of patients for whom cure is potentially achievable utilizing a multimodality approach. More aggressive treatment upfront with chemotherapy and ADT may improve the long term disease control. We hypothesize that Cabazitaxel may be added to radiation therapy safely, and we anticipate that this novel approach will improve disease control and eventually improve survival for locally advanced prostate cancer patients.


Condition Intervention Phase
Prostate Cancer
Drug: Cabazitaxel
Radiation: Intensity Modulated Radiation Therapy (IMRT)
Drug: Anti-Androgen Therapy: Bicalutamide
Genetic: Luteinizing Hormone-Releasing Hormone (LHRH) Agonist
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Weekly Cabazitaxel With Concurrent Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy for the Treatment of Locally Advanced High Risk Adenocarcinoma of the Prostate

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Maximally Tolerated Dose (MTD) of Cabazitaxel and Intensity Modulated Radiation Therapy (IMRT) [ Time Frame: Weekly during treatment then every 3 months until 2 years after completion of IMRT ] [ Designated as safety issue: Yes ]
    To determine the maximally tolerated dose, or the safety and feasibility, of the concurrent weekly Cabazitaxel and IMRT with androgen deprivation therapy


Secondary Outcome Measures:
  • Acute and Late Non-Hematologic and Hematologic Toxicity Profile of Cabazitaxel and Intensity Modulated Radiation Therapy (IMRT) Combination [ Time Frame: Weekly during IMRT, then at 2 weeks and 3 months after IMRT, and then every 3 months until 2 years after IMRT ] [ Designated as safety issue: Yes ]
    The toxicity profile will be recorded according to the NCI CTCAE v4.0 criteria. Toxicity assessment will be performed weekly during IMRT, then at 2 weeks and 3 months after IMRT, and then every 3 months until 2 years after IMRT.

  • 5-Year Biochemical Relapse Free Survival [ Time Frame: Within 5 years after completion of IMRT ] [ Designated as safety issue: No ]
    A PSA rise by 2 ng/mL or more above the nadir PSA is considered as biochemical relapse after external beam IMRT (ASTRO 2005 Phoenix criteria).


Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel with Intensity Modulated Radiation Therapy (IMRT)
Weekly Cabazitaxel with concurrent IMRT
Drug: Cabazitaxel

Administered weekly on the same day of radiation according to the following infusion levels:

Level 1 (Initial): 4 mg/m2; Level -1: 2 mg/m2; Level 2: 6 mg/m2; Level 3: 8 mg/m2; Level 4: 10 mg/2;

Other Names:
  • Cabazitaxel
  • Jevtana
  • XRP-6258
Radiation: Intensity Modulated Radiation Therapy (IMRT)
Starts 8 weeks after initiation of androgen deprivation therapy, given daily at 1.8 Gy for a total of 75.6 Gy
Other Names:
  • Intensity Modulated Radiation Therapy
  • IMRT
  • Radiation therapy
Drug: Anti-Androgen Therapy: Bicalutamide
  • Taken once daily by mouth starting between 2 weeks and 1 day before the first administration of Luteinizing Hormone-Releasing Hormone (LHRH)
  • Will continue once daily until the final day of IMRT
Other Names:
  • Casodex
  • Cosudex
  • Calutide
  • Kalumid
Genetic: Luteinizing Hormone-Releasing Hormone (LHRH) Agonist
  • First administration will occur 1 day to 2 weeks after the start of Bicalutamide and 8 weeks prior to the start of IMRT (+/- 4 weeks)
  • Will continue for 24 months after IMRT
  • Total administered duration and agent used must be documented on the case report form
Other Names:
  • Gonadotropin-releasing hormone
  • GnRH
  • LHRH
  • Luliberin

Detailed Description:

Patients with locally advanced high Gleason grade prostate cancer often have local and metastatic disease progression. To improve on these outcomes, therapy needs to be directed at controlling the androgen sensitive and insensitive prostate cancer cells in the primary and metastatic sites. This therapeutic challenge has further prompted the use of combined modality approaches incorporating chemotherapy and hormonal therapy with radiation aimed at the intrinsically resistant cells and the micrometastatic disease that are both androgen sensitive and resistant. High likelihood of occult metastatic disease and existence of intrinsically castration resistant cells are the main rationales for early institution of androgen deprivation therapy (ADT) and chemotherapy in prostate cancer.

The rationale for combining chemotherapeutic agents with ADT and radiotherapy in high risk prostate cancer patients is based on that chemotherapy can enhance radiotherapy and is also an effective therapy for metastatic castrate resistant disease. Prior studies with weekly docetaxel with ADT and intensity modulated radiation therapy (IMRT) were safe and feasible however cabazitaxel is more potent mitotic inhibitor which may further enhance the outcomes of patients with locally advanced prostate cancer.

Men with locally advanced high risk prostate cancer represent a group of patients for whom cure is potentially achievable utilizing a multimodality approach. More aggressive treatment upfront with chemotherapy and ADT would improve the long term disease control. We hypothesize that Cabazitaxel may be added to radiation therapy safely, and we anticipate that this novel approach will improve disease control and eventually improve survival for locally advanced prostate cancer patients.

The safety of the combination of Cabazitaxel with radiation will be established after this study. Potential efficacy will be determined in the future phase II/III trials. Hypofraction radiation treatment with shorter duration maybe possible if combined with chemotherapy modality.

  Eligibility

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

Inclusion Criteria:

  • Adenocarcinoma of the prostate with locally advanced prostate cancer without distant metastatic with unfavorable risk features that are defined below:
  • Gleason score ≥8
  • Gleason score 7 and T3/T4 disease
  • Gleason score 7 but PSA ≥20
  • Karnofsky Performance Status >70,
  • Age > 18
  • Performance Status: ECOG ≤2
  • Peripheral neuropathy: must be < grade 1
  • Hematologic (minimal values):
  • Absolute neutrophil count > 1,500/mm3
  • Hemoglobin > 8.0 g/dl
  • Platelet count > 100,000/mm3
  • Hepatic function
  • Total bilirubin < Upper limit of normal (ULN)(except for Gilbert's disease)
  • AST (SGOT) < 1.5 x ULN
  • ALT (SGPT) < 1.5 x ULN
  • Creatinine < 1.5 x ULN
  • Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
  • No history of previous chemotherapy or pelvic irradiation

Exclusion Criteria:

  • Patients with a history of severe hypersensitivity reaction to Cabazitaxel or other drugs formulated with polysorbate 80.
  • History of urological surgery or procedures predisposing to GU complications after radiation (will be determined by radiation oncologist)
  • History of diverticulitis, rectal bleeding or other lower GI diseases predisposing to GI complications after radiation (will be determined by radiation oncologist)
  • History of prior chemotherapy or pelvic irradiation,
  • History of prior invasive malignant cancer(s) within the last 5 years except adequately treated or controlled basal cell or squamous cell carcinoma of the skin
  • Documented distant metastatic disease.
  • Prior radical prostatectomy or cryosurgery for prostate cancer or bilateral orchiectomy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420250

Contacts
Contact: Jianqing Lin, MD 215-955-8874
Contact: Clinical Research Management Office 215-955-1661

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Jianqing Lin, MD    215-955-8874      
Contact: Clinical Research Management Office    215-955-1661      
Principal Investigator: Jianqing Lin, MD         
Sub-Investigator: William Kevin Kelly, DO         
Sub-Investigator: Jean Hoffman-Censits, MD         
Sub-Investigator: Adam Dicker, MD, PhD         
Sub-Investigator: Wenyin Shi, MD, PhD         
Sub-Investigator: Edouard Trabulsi, MD         
Sub-Investigator: Ruth Birbe, MD         
Sub-Investigator: Hushan Yang, PhD         
Sub-Investigator: Robert Den, MD         
Sub-Investigator: Mark Hurwitz, MD         
Sponsors and Collaborators
Thomas Jefferson University
Sanofi
Investigators
Principal Investigator: Jianqing Lin, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01420250     History of Changes
Other Study ID Numbers: 11D.243, 2011-32
Study First Received: August 17, 2011
Last Updated: March 10, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Prostate cancer
Adenocarcinoma of the prostate

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgen Antagonists
Bicalutamide
Androgens
Hormones
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014