Androgen Ablation Therapy With or Without Chemotherapy in Treating Patients With Metastatic Prostate Cancer - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00309985

Purpose

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen ablation therapy may stop the adrenal glands from making androgens. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether androgen ablation therapy is more effective with or without docetaxel in treating metastatic prostate cancer.

PURPOSE: This randomized phase III trial is studying androgen ablation therapy and chemotherapy to see how well they work compared to androgen ablation therapy alone in treating patients with metastatic prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: docetaxel Procedure: antiandrogen therapy	Phase III

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Docetaxel

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer [CHAARTED]

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Prostate-specific antigen (PSA) response [ Designated as safety issue: No ]
Change in PSA over time [ Designated as safety issue: No ]
Time to hormone refractory disease [ Designated as safety issue: No ]
Time to clinical progression [ Designated as safety issue: No ]
Time to PSA progression [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	600
Study Start Date:	July 2006
Estimated Primary Completion Date:	April 2024 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Experimental Patients receive androgen deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: docetaxel Given IV Procedure: antiandrogen therapy No information provided
Arm B: Active Comparator Patients receive androgen deprivation therapy (as in arm A) alone.	Procedure: antiandrogen therapy No information provided

Detailed Description:

OBJECTIVES:

Primary

Evaluate the ability of early chemotherapy to improve overall survival of patients commencing androgen deprivation for metastatic prostate cancer.

Secondary

Determine whether early chemotherapy can increase the time to clinical progression (radiographic or symptomatic deterioration due to disease) over hormonal therapy alone.
Determine whether early chemotherapy can increase the time to development of hormone-refractory disease over hormonal therapy alone.
Determine whether early chemotherapy can increase the time to serological progression over hormonal therapy alone.
Determine rates of biochemical response at 6 months and 12 months in the chemohormonal arm versus the hormonal therapy alone arm.
Determine the frequency of adverse events and the tolerability of chemotherapy combined with hormonal therapy versus hormonal therapy alone.
Determine whether the postulated clinically meaningful increase in disease control is associated with an alteration in overall quality of life using the Functional Assessment of Cancer Therapy-Prostate questionnaire.
Determine the ability of prostate-specific antigen changes to be a surrogate for clinical benefit from therapy and overall survival.

Tertiary

Determine whether there are proteins differentially translated from the genome in hormone-sensitive prostate cancer, prostate cancer that has responded to hormonal therapy, and hormone-refractory prostate cancer.
Determine the frequency of constitutive polymorphisms of enzymes involved in steroid metabolism and other carcinogenic processes.
Determine whether the amount and frequency of certain carcinogenic proteins in prostate cancer tissue such as CXCR4 and manganese superoxide dismutase can be correlated with a poor prognosis.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (≥ 70 vs < 70), ECOG performance status (0-1 vs 2), combined androgen blockade for > 30 days (yes vs no), duration of prior adjuvant hormonal therapy (> 12 months vs ≤ 12 months), concurrent bisphosphonate use (yes vs no), and volume of disease (low vs high). Patients are randomized to 1 of 2 treatment arms.

Arm A: Patients receive androgen deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Arm B: Patients receive androgen deprivation therapy (as in arm A) alone. Quality of life is assessed at baseline and at weeks 12, 24, 36, and 48.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 568 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed prostate cancer
- High-volume metastatic disease meeting any of the following criteria:
  - Visceral metastases (extranodal)
  - Bone metastases
    - At least 4 bone lesions
    - At least 1 bone lesion must be outside of the vertebral column or pelvis
On androgen deprivation therapy for < 120 days
- Prostate-specific antigen (PSA) level may not have risen > 50% from its lowest point between the start of androgen deprivation therapy and randomization

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2
- PS 2 eligible only if decline in PS is due to metastatic prostate cancer
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ upper limit of normal (ULN)
ALT ≤ 2.5 times ULN
Creatinine clearance ≥ 30 mL/min
PT and INR ≤ 1.5 times ULN (unless on therapeutic anticoagulation)
PTT ≤ 1.5 times ULN (unless on therapeutic anticoagulation)
No prior malignancy in the past 5 years except for basal cell or squamous cell carcinoma of the skin
- Other malignancies that are considered to have low potential to progress (e.g., grade 2, T1a transitional cell carcinoma) may be allowed if approved by study chair
No peripheral neuropathy > grade 1
No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
No active cardiac disease, including the following:
- Active angina
- Symptomatic congestive heart failure
- Myocardial infarction within the past 6 months
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 4 weeks since prior major surgery and recovered from all toxicity prior to randomization
Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following are true:
- At least 12 months since prior therapy with no evidence of disease, defined as 1 of the following:
  - PSA < 0.1 ng/dL after prostatectomy plus hormonal therapy
  - PSA < 0.5 ng/dL and has not doubled above nadir after radiotherapy plus hormonal therapy
- No more than 24 months of prior therapy
  - Last depot injection must have expired by the 24-month mark
Prior palliative radiotherapy allowed if commenced within 30 days before starting androgen deprivation
Anti-androgen therapy allowed as single-agent therapy ≤ 7 days before medial castration to prevent flare
No prior chemotherapy in adjuvant or neoadjuvant setting
No prior hormone therapy in the metastatic setting
More than 30 days (or 6 half-lives) (whichever is longer) since prior participation in another clinical trial
Concurrent participation in nontherapeutic trials allowed
Concurrent antiandrogen therapy (e.g., bicalutamide or flutamide) allowed, but not as sole hormonal therapy
No concurrent 5-alpha reductase inhibitors

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00309985

Show 221 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Christopher Sweeney, MBBS	Indiana University Melvin and Bren Simon Cancer Center
Investigator:	David Jarrard, MD	University of Wisconsin, Madison

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000462099, ECOG-E3805
Study First Received:	March 29, 2006
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00309985
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent prostate cancer
stage IV prostate cancer

Study placed in the following topic categories:

Docetaxel
Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms

Genital Diseases, Male
Prostatic Neoplasms
Recurrence

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 14, 2009