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Androgen Ablation Therapy With or Without Chemotherapy in Treating Patients With Metastatic Prostate Cancer (CHAARTED)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT00309985
First received: March 29, 2006
Last updated: February 1, 2016
Last verified: February 2016
  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
Metastatic Hormone-sensitive Prostate Cancer
Drug: androgen-deprivation therapy
Drug: docetaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to death or date last known alive. Survival data reflects the database as of December 23, 2013.


Secondary Outcome Measures:
  • Time to Clinical Progression [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry ] [ Designated as safety issue: No ]
    Time to clinical progression is defined as the time from randomization to clinical progression. Clinical progression is defined as increasing symptomatic bone metastases, progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria or clinical deterioration due to cancer per investigator's opinion. Patients without documented clinical progression were censored at the date of last disease assessment. Secondary endpoint data reflect the database as of December 23, 2014.

  • Time to Castration Resistant Prostate Cancer (Hormone Refractory Disease) [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry ] [ Designated as safety issue: No ]
    Time to castration resistant prostate cancer is defined as the time from randomization to PSA progression or clinical progression, whichever occurred first. Patients without documented progression were censored at the date of last disease assessment. Secondary endpoint data reflect the database as of December 23, 2014.

  • Proportion of Patients With PSA Complete Response (CR) at 6 Months [ Time Frame: Assessed at 6 months ] [ Designated as safety issue: No ]
    PSA CR is defined as a PSA level less than 0.2 ng/ml measured for 2 consecutive measurements at least 4 weeks apart. Patients who met the criterion of PSA CR and had PSA level less than 0.2 ng/ml before and after the 6-month time point are considered as having a PSA CR at 6 months.

  • Proportion of Patients With PSA Complete Response (CR) at 12 Months [ Time Frame: Assessed at 12 months ] [ Designated as safety issue: No ]
    PSA CR is defined as a PSA level less than 0.2 ng/ml measured for 2 consecutive measurements at least 4 weeks apart. Patients who met the criterion of PSA CR and had PSA level less than 0.2 ng/ml before and after the 12-month time point are considered as having a PSA CR at 12 months.

  • QOL Change From Baseline to 3 Months [ Time Frame: Assessed at baseline and 3 months ] [ Designated as safety issue: No ]
    The primary QOL change was evaluated by the Functional Assessment of Cancer Therapy - Prostate (FACT-P) instrument. FACT-P is a self-report measure of both general and disease-specific QOL. Higher scores represent better QOL. The FACT-P (version 4) contains 39 likert items distributed over 5 subscales: physical (7 items), social/family (7 items), emotional (6 items), and functional (7 items) well-being, and the additional concerns related to prostate cancer scale (12 items). The FACT-P total score is calculated by summing all these 5 subscales and ranges from 0 to 156.


Enrollment: 790
Study Start Date: July 2006
Estimated Study Completion Date: December 2022
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Androgen-Deprivation Therapy and Docetaxel
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: androgen-deprivation therapy
LHRH analogs are administered with a variety of techniques such as subcutaneously, intramuscularly, or insertion, while antiandrogens (flutamide and bicalutamide) were given orally.
Drug: docetaxel
Given IV
Other Names:
  • Taxotere
  • RP 56976
  • NSC #628503
Active Comparator: Androgen-Deprivation Therapy alone
Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration) alone.
Drug: androgen-deprivation therapy
LHRH analogs are administered with a variety of techniques such as subcutaneously, intramuscularly, or insertion, while antiandrogens (flutamide and bicalutamide) were given orally.

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 (PSA) 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 C-X-C chemokine receptor type 4 (CXCR-4) 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 (Androgen-Deprivation Therapy and Docetaxel): Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel intravenously (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 (Androgen-Deprivation Therapy alone): Patients receive androgen-deprivation therapy (as in arm A) alone.

Quality of life is assessed at baseline and at months 3, 6, 9 and 12.

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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed prostate cancer
  • Metastatic disease
  • On androgen-deprivation therapy for < 120 days
  • Eastern Cooperative Oncology Group (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)
  • Alanine aminotransferase (ALT) ≤ 2.5 times ULN
  • Creatinine clearance ≥ 30 mL/min
  • Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 times ULN (unless on therapeutic anticoagulation)
  • Partial thromboplastin time (PTT) ≤ 1.5 times ULN (unless on therapeutic anticoagulation)
  • Fertile patients must use effective contraception
  • 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:

    • Therapy was discontinued ≥ 12 months ago AND there is no evidence of disease, as defined by 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
    • Therapy lasted no more than 24 months

      • 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
  • 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

Exclusion Criteria:

  • Prostate-specific antigen (PSA) level has risen and met criteria for progression from its lowest point between the start of androgen-deprivation therapy and randomization
  • 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
  • Peripheral neuropathy > grade 1
  • History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
  • Active cardiac disease, including the following:

    • Active angina
    • Symptomatic congestive heart failure
    • Myocardial infarction within the past 6 months
  • Prior chemotherapy in adjuvant or neoadjuvant setting
  • Prior hormone therapy in the metastatic setting
  • Concurrent 5-alpha reductase inhibitors
  • Simultaneous enrollment on Cancer and Leukemia Group B (CALGB) 90202
  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: NCT00309985

  Show 343 Study Locations
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Study Chair: Christopher Sweeney, MBBS Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT00309985     History of Changes
Other Study ID Numbers: E3805  E3805  U10CA180794 
Study First Received: March 29, 2006
Results First Received: December 17, 2015
Last Updated: February 1, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Keywords provided by Eastern Cooperative Oncology Group:
metastatic hormone-sensitive prostate cancer
docetaxel

Additional relevant MeSH terms:
Prostatic Neoplasms
Hypersensitivity
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Immune System Diseases
Docetaxel
Methyltestosterone
Hormones
Estrogens, Conjugated (USP)
Prolactin Release-Inhibiting Factors
Androgens
Ascorbic Acid
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antioxidants
Protective Agents
Vitamins
Micronutrients
Growth Substances
Estrogens
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on September 27, 2016