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

• ClinicalTrials.gov Identifier: NCT00309985
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2006
• Results First Posted: March 3, 2016
• Last Update Posted: March 18, 2024
• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Tracking Information

• First Submitted Date: March 29, 2006
• First Posted Date: April 3, 2006
• Results First Submitted Date: December 17, 2015
• Results First Posted Date: March 3, 2016
• Last Update Posted Date: March 18, 2024
• Actual Study Start Date: September 26, 2006
• Actual Primary Completion Date: December 23, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2016)

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 ]

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 1, 2016)

• 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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Androgen Ablation Therapy With or Without Chemotherapy in Treating Patients With Metastatic Prostate Cancer
• Official Title: CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer

Brief Summary

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.

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Hormone-sensitive Prostate Cancer

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Drug: androgen-deprivation therapy
  • Drug: docetaxel
• 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.
  Intervention: Drug: androgen-deprivation therapy

Publications *

• Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5.
• Lage DE, Michaelson MD, Lee RJ, Greer JA, Temel JS, Sweeney CJ. Outcomes of older men receiving docetaxel for metastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis. 2021 Dec;24(4):1181-1188. doi: 10.1038/s41391-021-00389-2. Epub 2021 May 18.
• Martini A, Pfail J, Montorsi F, Galsky MD, Oh WK. Surrogate endpoints for overall survival for patients with metastatic hormone-sensitive prostate cancer in the CHAARTED trial. Prostate Cancer Prostatic Dis. 2020 Dec;23(4):638-645. doi: 10.1038/s41391-020-0231-5. Epub 2020 Apr 20.
• Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of Life During Treatment With Chemohormonal Therapy: Analysis of E3805 Chemohormonal Androgen Ablation Randomized Trial in Prostate Cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. doi: 10.1200/JCO.2017.75.3335. Epub 2018 Mar 9.
• Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. doi: 10.1200/JCO.2017.75.3657. Epub 2018 Jan 31.
• Harshman LC, Chen YH, Liu G, Carducci MA, Jarrard D, Dreicer R, Hahn N, Garcia JA, Hussain M, Shevrin D, Eisenberger M, Kohli M, Plimack ER, Cooney M, Vogelzang NJ, Picus J, Dipaola R, Sweeney CJ; ECOG-ACRIN 3805 Investigators. Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel. J Clin Oncol. 2018 Feb 1;36(4):376-382. doi: 10.1200/JCO.2017.75.3921. Epub 2017 Dec 20.
• Scott E. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Department of Medicine; Department of Biostatistics and Computational Biology; Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Johns Hopkins University, Baltimore; University of Wisconsin Carbone Cancer Center; School of Medicine and Public Health; Madison; Fox Chase Cancer Center, Temple University Health System, Philadelphia; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis; Mayo Clinic, Rochester, MN; University Hospitals Case Medical Center, Seidman Cancer Center; Cleveland Clinic Taussig Cancer Institute; Both in Cleveland; University of Virginia Cancer Center, Charlottesville; Comprehensive Cancer Centers of Nevada, Las Vegas; Siteman Cancer Center, Washington University School of Medicine, St. Louis; NorthShore University Health System, Evanston, IL; University of Michigan Comprehensive Cancer Center, Ann Arbor; Rutgers Cancer Institute of New Jersey, New Brunswick.N Engl J Med. 2015 Aug 20;373(8):737-46. [Epub 2015 Aug 5]. doi: 10.1056/NEJMoa1503747. Urol Oncol. 2017 Mar;35(3):123. doi: 10.1016/j.urolonc.2016.12.021. Epub 2017 Feb 1.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 1, 2016): 790
• Original Enrollment: Not Provided
• Estimated Study Completion Date: July 2024
• Actual Primary Completion Date: December 23, 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States
• Removed Location Countries: Peru, Puerto Rico

Administrative Information

• NCT Number: NCT00309985
• Other Study ID Numbers: E3805; E3805 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); U10CA180794 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

• Current Responsible Party: Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
• Original Responsible Party: Not Provided
• Current Study Sponsor: ECOG-ACRIN Cancer Research Group
• Original Study Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Christopher Sweeney, MBBS; Dana-Farber Cancer Institute

• PRS Account: Eastern Cooperative Oncology Group
• Verification Date: March 2024