Surgery With or Without Docetaxel and Leuprolide or Goser... | NCT00430183

ID	Type	Description	Link
U10CA031946	U.S. NIH Grant/Contract		View source
CDR0000526353	Other Identifier	Physician Data Query

Status Module

Name	Class
National Cancer Institute (NCI)	NIH
Eastern Cooperative Oncology Group	NETWORK
NCIC Clinical Trials Group	NETWORK
SWOG Cancer Research Network

Description Module

Detailed Description

This randomized trial tests whether the addition of chemohormonal therapy improves PSA-progression free survival in patients with high risk, clinically-localized prostate cancer. The neoadjuvant approach is taken since there appears to be a higher acceptance rate in the prostate population for this type of therapy and several phase II trials have demonstrated its safety. Multiple chemotherapeutic therapies have shown efficacy in advanced prostate cancer and docetaxel has become the community standard. Many high risk patients are initiated on LHRH agonists at or near the time of diagnosis of their prostate cancer. In order to allow the inclusion of these patients in the protocol, enhanced enrollment and maintain compliance with therapy, up to 3 months of androgen deprivation therapy prior to enrollment will be permitted. This study will therefore be able to test the hypothesis that targeting both androgen-sensitive and chemotherapy- sensitive prostate cancer cells will improve outcomes in these high-risk patients.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to nomogram-predicted biochemical progression-free survival at 5 years (0-20.9% vs 21-39.9% vs 40-59.9% vs ≥ 60%) and androgen-deprivation therapy prior to randomization ≤ 4 months (no vs yes). Patients are randomized to 1 of 2 treatment arms. Please see the Arms sections for more details.

The primary and secondary objectives are described below.

Primary:

- To determine whether treatment with neoadjuvant docetaxel and androgen deprivation therapy prior to radical prostatectomy will increase the rate of 3-year biochemical progression-free survival (bPFS) compared to treatment with immediate radical prostatectomy alone for high-risk prostate cancer patients.

Secondary:

To compare the 5-year bPFS rate, bPFS, disease progression, disease-free survival, and overall survival of patients randomized to the two arms of this trial
To determine the safety and tolerability of neoadjuvant docetaxel and androgen deprivation therapy prior to surgery for high-risk patients undergoing radical prostatectomy
To compare the impact of neoadjuvant docetaxel and androgen deprivation therapy on time to clinically apparent local disease recurrence and metastatic disease in high-risk patients undergoing radical prostatectomy for clinically localized prostate cancer
To compare the impact of neoadjuvant docetaxel and androgen deprivation therapy relative to RP on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for high-risk patients undergoing radical prostatectomy for clinically localized prostate cancer
To determine if changes in serum testosterone levels will predict bPFS
To determine prospectively whether PSA doubling time (PSADT) is a surrogate endpoint for time to clinical metastases and overall survival

Patients are followed up to 15 years post-randomization.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: docetaxel + LHRH agonist + surgical intervention	Experimental	Patients receive six cycles of docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines. Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.	Drug: docetaxel Drug: LHRH agonist Procedure: surgery
Arm B: surgical intervention	Other	All patients undergo standard surgical intervention. The surgical procedures will be performed within 60 days of randomization. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. Adjuvant radiation must be initiated within 6 months of the date of surgery.	Procedure: surgery

Interventions

Name	Type	Description	Arm Group Labels	Other Names
docetaxel	Drug	75 mg/m^2 will be administered intravenously over one hour on Day 1 of each cycle, every 21 days	Arm A: docetaxel + LHRH agonist + surgical intervention

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Biochemical Progression-Free Survival (bPFS Proportion) at 3 Years	Proportion of participants surviving 3 years from randomization without biochemical progression or death. bPFS was defined as the time from randomization to the date of the first documented biochemical progression or death. Progression will be defined as having experienced either of the following: a serum PSA level > 0.2 ng/mL that increases on 2 consecutive occasions each of which is at least 3 months apart or death occurs. The time of biochemical failure is measured from the date of randomization to the date of the first PSA level > 0.2 ng/mL.	Up to 3 years

Secondary Outcomes

Measure	Description	Time Frame
5-year bPFS Rate	Proportion of participants surviving 5 years from randomization without biochemical progression or death.	5 years
Time to Clinical Local Recurrence (The Time From Randomization to the First Biopsy-proven Recurrence in the Prostatic Bed or New Mass.)

Eligibility Module

Eligibility Criteria

Histologic documentation - Histologic documentation of prostatic adenocarcinoma.

Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible.

All eligible patients must have a known Gleason sum based on biopsy or TURP at the time of registration.
Clinically localized disease - Patients must have clinical stage T1-T3a and no radiographic evidence of metastatic disease as demonstrated by:
- EITHER CT or MRI of the abdomen and pelvis, OR endorectal MRI of the pelvis that demonstrate no nodes > 1.5 cm. If one or more pelvic lymph node(s) measures > 1.5 cm, a negative biopsy is required. If more than one lymph node is > 1.5 cm, the largest or most accessible node should be biopsied.
AND
- Negative bone scan (with plain films and/or MRI and/or CT scan confirmation, if necessary). Positive PET and Prostascint scans are not considered proof of metastatic disease.
Determination of high-risk status: Patients must have either:
- A Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of < 60%.
OR
- Prostate biopsy Gleason sum ≥ 8 (NOTE: The Kattan nomogram probability must be calculated for all patients, including those eligible based on Gleason sum ≥ 8 only.)
Prior treatment - No prior treatment for prostate cancer including prior surgery (excluding TURP), pelvic lymph node dissection, radiation therapy, or chemotherapy.

Patients may have received up to 4 months of androgen deprivation therapy (LHRH agonists, antiandrogens, or both) prior to being enrolled on the study.
Appropriate surgical candidates - Patients must be appropriate candidates for radical prostatectomy with an estimated life expectancy > 10 years as determined by a urologist. Evidence of underlying cardiac disease should be evaluated prior to enrollment to ensure that patients are not at high risk of cardiac complications.
Clotting history - Patients with a history of deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident or currently requiring systemic anticoagulation are eligible provided they are determined to be candidates for radical prostatectomy.
ECOG performance status: 0-2
Age: ≥ 18 years of age
Required Initial Laboratory Values:
- ANC ≥ 1500/μL
- Platelet count ≥ 150,000/μL
- Creatinine ≤ 2.0 mg/dL
- Pre-registration serum PSA level ≤ 100 ng/mL
- Bilirubin ≤ 1.5XULN (2.5XULN in patients with Gilbert's disease)
- AST/ALT ≤1.5XULN

Name	Affiliation	Role
James Eastham, MD	Memorial Sloan Kettering Cancer Center	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Providence Cancer Center		Anchorage	Alaska	99508	United States
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital

PubMed Identifier	Type	Citation	Retractions
32706639	Derived	Eastham JA, Heller G, Halabi S, Monk JP 3rd, Beltran H, Gleave M, Evans CP, Clinton SK, Szmulewitz RZ, Coleman J, Hillman DW, Watt CR, George S, Sanda MG, Hahn OM, Taplin ME, Parsons JK, Mohler JL, Small EJ, Morris MJ. Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer. J Clin Oncol. 2020 Sep 10;38(26):3042-3050. doi: 10.1200/JCO.20.00315. Epub 2020 Jul 24.

Label	URL
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A: Docetaxel + LHRH Agonist + Surgical Intervention	Patients receive six cycles of 75 mg/m^2 docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines.Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 11, 2018

Arm/Group Information

ID	Title	Description
BG000	Arm A: Docetaxel + LHRH Agonist + Surgical Intervention	Patients receive six cycles of 75 mg/m^2 docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines.> > Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. > > Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.
BG001	Arm B: Surgical Intervention	All patients undergo standard surgical intervention. The surgical procedures will be performed within 60 days of randomization. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. Adjuvant radiation must be initiated within 6 months of the date of surgery (surgery: Patients undergo radical prostatectomy with staging pelvic lymphadenectomy).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00062(40 to 78) BG00163(33 to 84) BG00263(33 to 84)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
White	BG000330 BG001337 BG002

Clinical stage by digital rectal examination (Primary Tumor (T) Stage)

The stage of cancer (amount or spread of cancer in the body) that is based on digital rectal examination performed prior to surgery. The primary tumor (T) stage using the TNM system is reported here. TX: Main tumor cannot be measured.>> T0: Main tumor cannot be found.>> T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
T1	BG000102 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Biochemical Progression-Free Survival (bPFS Proportion) at 3 Years

Proportion of participants surviving 3 years from randomization without biochemical progression or death. bPFS was defined as the time from randomization to the date of the first documented biochemical progression or death. Progression will be defined as having experienced either of the following: a serum PSA level > 0.2 ng/mL that increases on 2 consecutive occasions each of which is at least 3 months apart or death occurs. The time of biochemical failure is measured from the date of randomization to the date of the first PSA level > 0.2 ng/mL.

Posted

Number

95% Confidence Interval

proportion of patients

Up to 3 years

ID	Title	Description
OG000	Arm A: Docetaxel + LHRH Agonist + Surgical Intervention	Patients receive six cycles of 75 mg/m^2 docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines.> > Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. > > Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.
OG001	Arm B: Surgical Intervention	All patients undergo standard surgical intervention. The surgical procedures will be performed within 60 days of randomization. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. Adjuvant radiation must be initiated within 6 months of the date of surgery (surgery: Patients undergo radical prostatectomy with staging pelvic lymphadenectomy).

Units	Counts
Participants	OG000391 OG001397

Title

Denominators

Categories

Title	Measurements
	OG0000.89(0.87 to 0.91) OG0010.84(0.78 to 0.90)

Secondary

5-year bPFS Rate

Proportion of participants surviving 5 years from randomization without biochemical progression or death.

Posted

Number

Proportion of participants

5 years

ID	Title	Description
OG000	Arm A: Docetaxel + LHRH Agonist + Surgical Intervention	Patients receive six cycles of 75 mg/m^2 docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines.Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.
OG001	Arm B: Surgical Intervention	All patients undergo standard surgical intervention. The surgical procedures will be performed within 60 days of randomization. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. Adjuvant radiation must be initiated within 6 months of the date of surgery(surgery: Patients undergo radical prostatectomy with staging pelvic lymphadenectomy).

Secondary

Time to Clinical Local Recurrence (The Time From Randomization to the First Biopsy-proven Recurrence in the Prostatic Bed or New Mass.)

Not Posted

Oct 2030