Docetaxel, Androgen Ablation, and External-Beam Radiation Therapy in Patients With High-Risk Localized Prostate Cancer (NRR)

• ClinicalTrials.gov Identifier: NCT00225420
• Recruitment Status: Completed
• First Posted: September 23, 2005
• Results First Posted: June 1, 2017
• Last Update Posted: June 1, 2017
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborator: Sanofi
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer
• Interventions: Drug: docetaxel; Drug: leuprolide acetate; Radiation: radiation therapy
• Enrollment: 23

Participant Flow

Recruitment Details	Subjects with high-risk or locally advanced prostate cancer were recruited from 2 institutions between December 2005 and January 2010.
Pre-assignment Details	Two patients were taken off the study due illness, two were removed because they were too large for the equipment, and one was removed due to CT screen failure.18 men with high-risk or locally advanced prostate cancer were enrolled. All 18 patients completed their radiation therapy and 16 completed all planned chemotherapy doses.

Arm/Group Title	Docetaxel 10 mg/m2	Docetaxel 15 mg/m2	Docetaxel 20 mg/m2
Arm/Group Description	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 10 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg intramuscular (IM) and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 centigray (cGy) in 200 cGy per fraction for a total of 39 treatments.	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 15 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg intramuscular (IM) and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 20 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg intramuscular (IM) and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments
Period Title: Overall Study
Started	9	6	3
Completed	9	6	3
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		Overall Study
Arm/Group Description		Single Arm Docetaxel: Docetaxel will be administered per the designated cohort starting at 10, 15 or 20 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments.
Overall Number of Baseline Participants		18
Baseline Analysis Population Description		All patients included in this trial were high-risk localized (Gleason 8-10 or PSA level >= 20 ng/mL) prostate cancer, or T3 disease.
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	18 participants
		62; (45 to 77)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	Female	0 0.0%
	Male	18 100.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	4 22.2%
	White	14 77.8%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	18 participants
		18
Clinical Stage [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	T1c-T2a	9 50.0%
	T2b-T2c	5 27.8%
	T3	4 22.2%
		[1] Measure Description: The Classification of Malignant Tumours (TNM) system is a widely used cancer staging system. The T refers to the size and extent of the main tumor. The main tumor is usually called the primary tumor. T0 means the main tumor cannot be found. The higher the number following T, the larger the tumor or the more it has grown.
Gleason Score [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	18 participants
Grade 7		3 16.7%
Grade 8-10		15 83.3%
		[1] Measure Description: A Gleason score is given based on how the prostate cancer tissue looks under the microscope. Gleason scores range from 2 to 10 and indicates how likely the tumor will spread. The higher the Gleason score the more likely the cancer tissue will spread.
PSA level, ng/mL [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	<10 ng/mL	6 33.3%
	10-19 ng/mL	4 22.2%
	20-100 ng/mL	5 27.8%
	>100 ng/mL	3 16.7%
		[1] Measure Description: Prostate-specific antigen (PSA) is a protein produced by cells of the prostate gland. The PSA test measures the level of PSA in the blood. PSA levels are often elevated in men with prostate cancer.

Outcome Measures

1. Primary Outcome

Title	Number of Patients Experiencing Dose-Limiting Toxicities
Description	Determine the number of patients experiencing dose-limiting toxicities (DLT) at each dose level. DLT was defined as grade 3-4 non-haematological or grade 4 haematological toxicity, using the Common Terminology Criteria for Adverse Events, version 3.0.
Time Frame	Average follow up of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel at 10 mg/m2	Docetaxel 15 mg/m2	Docetaxel 20 mg/m2
Arm/Group Description:	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 10 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments.	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 15 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 20 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments
Overall Number of Participants Analyzed	9	6	3
Measure Type: Count of Participants; Unit of Measure: Participants
	1	1	0

2. Secondary Outcome

Title	Biochemical Progression-free Survival (PFS)
Description	Measure of the activity of a treatment on a disease. In this study it is measured from the date of enrollment to the date on which the prostate cancer progresses or the date the patient dies. Survival curves were estimated using the Kaplan-Meier technique. Biochemical (PSA) failure is defined, in accordance to the American Society for Therapeutic Radiology and Oncology consensus definition, as three consecutive rise in PSA. The date of biochemical failure is considered to be the midpoint between the last non-rising PSA and the first rising PSA.
Time Frame	Average follow up of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description:	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 10 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments.
Overall Number of Participants Analyzed	18
Mean (95% Confidence Interval); Unit of Measure: percentage of patients
	94; (65 to 99)

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Single Arm
Arm/Group Description	Single Arm docetaxel: Docetaxel will be administered per the designated cohort starting at 10 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments. leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel. radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments.
All-Cause Mortality
	Single Arm
	Affected / at Risk (%)
Total	0/18 (0.00%)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)
Total	0/18 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Single Arm
	Affected / at Risk (%)
Total	18/18 (100.00%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (Specify, __) * 1 [1]	1/18 (5.56%)
Hemoglobin * 1	12/18 (66.67%)
Cardiac disorders
Hypertension * 1	5/18 (27.78%)
Pain - Chest/thorax NOS * 1	1/18 (5.56%)
Supraventricular and nodal arrhythmia - Sinus tachycardia * 1	1/18 (5.56%)
Endocrine disorders
Hot flashes/flushes * 1	10/18 (55.56%)
Gastrointestinal disorders
Constipation * 1	6/18 (33.33%)
Diarrhea * 1	8/18 (44.44%)
Distension/bloating, abdominal * 1	3/18 (16.67%)
Dry mouth/salivary gland (xerostomia) * 1	1/18 (5.56%)
Flatulence * 1	1/18 (5.56%)
Gastrointestinal - Other (Specify, __) * 1 [2]	1/18 (5.56%)
Heartburn/dyspepsia * 1	2/18 (11.11%)
Hemorrhage, GI - Abdomen NOS * 1	1/18 (5.56%)
Hemorrhoids * 1	3/18 (16.67%)
Incontinence, anal * 1	1/18 (5.56%)
Nausea * 1	6/18 (33.33%)
Pain - Abdomen NOS * 1	1/18 (5.56%)
Pain - Rectum * 1	1/18 (5.56%)
Pain - Stomach * 1	1/18 (5.56%)
Proctitis * 1	1/18 (5.56%)
Ulcer, GI - Anus * 1	1/18 (5.56%)
Vomiting * 1	1/18 (5.56%)
General disorders
Constitutional Symptoms (Other, specify) * 1 [3]	1/18 (5.56%)
Edema: head and neck * 1	1/18 (5.56%)
Edema: limb * 1	1/18 (5.56%)
Fatigue (asthenia, lethargy, malaise) * 1	11/18 (61.11%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) * 1	1/18 (5.56%)
Flu-like syndrome * 1	1/18 (5.56%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever) * 1	1/18 (5.56%)
Cytokine release syndrome/acute infusion reaction * 1	1/18 (5.56%)
Infections and infestations
Infection - Other (Specify, __) * 1 [4]	1/18 (5.56%)
Investigations
Alkaline phosphatase * 1	4/18 (22.22%)
Leukocytes (total WBC) * 1	4/18 (22.22%)
Lymphopenia * 1	12/18 (66.67%)
Neutrophils/granulocytes (ANC/AGC) * 1	2/18 (11.11%)
Platelets * 1	6/18 (33.33%)
Weight gain * 1	2/18 (11.11%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia) * 1	4/18 (22.22%)
ALT, SGPT (serum glutamic pyruvic transaminase) * 1	2/18 (11.11%)
AST, SGOT(serum glutamic oxaloacetic transaminase) * 1	1/18 (5.56%)
Bicarbonate, serum-low * 1	1/18 (5.56%)
Bilirubin (hyperbilirubinemia) * 1	1/18 (5.56%)
Calcium, serum-high (hypercalcemia) * 1	1/18 (5.56%)
Cholesterol, serum-high (hypercholesteremia) * 1	1/18 (5.56%)
Creatinine * 1	1/18 (5.56%)
Glucose, serum-high (hyperglycemia) * 1	7/18 (38.89%)
Magnesium, serum-high (hypermagnesemia) * 1	5/18 (27.78%)
Phosphate, serum-low (hypophosphatemia) * 1	1/18 (5.56%)
Potassium, serum-high (hyperkalemia) * 1	2/18 (11.11%)
Potassium, serum-low (hypokalemia) * 1	1/18 (5.56%)
Sodium, serum-low (hyponatremia) * 1	1/18 (5.56%)
Triglyceride, serum-high (hypertriglyceridemia) * 1	1/18 (5.56%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic) * 1	1/18 (5.56%)
Musculoskeletal/Soft Tissue - Other (Specify, __) * 1 [5]	2/18 (11.11%)
Pain - Back * 1	2/18 (11.11%)
Pain - Joint * 1	1/18 (5.56%)
Pain - Neck * 1	1/18 (5.56%)
Pain - Other (Specify, __) * 1 [6]	1/18 (5.56%)
Nervous system disorders
Dizziness * 1	4/18 (22.22%)
Neuropathy: sensory * 1	3/18 (16.67%)
Pain - Head/headache * 1	3/18 (16.67%)
Taste alteration (dysgeusia) * 1	2/18 (11.11%)
Vasovagal episode * 1	1/18 (5.56%)
Psychiatric disorders
Insomnia * 1	7/18 (38.89%)
Mood alteration - Anxiety * 1	2/18 (11.11%)
Mood alteration - Depression * 1	1/18 (5.56%)
Renal and urinary disorders
Bladder spasms * 1	1/18 (5.56%)
Pain - Bladder * 1	1/18 (5.56%)
Renal/Genitourinary - Other (Specify, __) * 1 [7]	6/18 (33.33%)
Urinary frequency/urgency * 1	14/18 (77.78%)
Urinary retention (including neurogenic bladder) * 1	2/18 (11.11%)
Reproductive system and breast disorders
Erectile dysfunction * 1	1/18 (5.56%)
Libido * 1	1/18 (5.56%)
Pain - Penis * 1	1/18 (5.56%)
Respiratory, thoracic and mediastinal disorders
Apnea * 1	1/18 (5.56%)
Cough * 1	2/18 (11.11%)
Dyspnea (shortness of breath) * 1	5/18 (27.78%)
Pulmonary/Upper Respiratory - Other (Specify, __) * 1 [8]	2/18 (11.11%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis) * 1	1/18 (5.56%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, __) * 1 [9]	3/18 (16.67%)
Dry skin * 1	1/18 (5.56%)
Rash: acne/acneiform * 1	4/18 (22.22%)
Skin breakdown/decubitus ulcer * 1	1/18 (5.56%)
1 Term from vocabulary, CTCAE (3.0); * Indicates events were collected by non-systematic assessment; [1] decreased red blood cells; [2] Gastroesophageal reflux disease (GERD).; [3] Cold sensitivity; [4] Cold Symptoms; [5] leg cramps; [6] Left shoulder; [7] Dysuria; painful urination; intermittent bladder spasms; [8] Cold/upper respiratory infection; [9] Fungal infection

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Robin V. Johnson
• Organization: Lineberger Comprehensive Cancer Center
• Phone: 919-966-1125
• EMail: robin_v_johnson@med.unc.edu

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00225420
• Other Study ID Numbers: LCCC 0420
• First Submitted: September 21, 2005
• First Posted: September 23, 2005
• Results First Submitted: March 9, 2017
• Results First Posted: June 1, 2017
• Last Update Posted: June 1, 2017