Doce/Enza: Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer

• Sponsor: Prostate Cancer Clinical Trials Consortium (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02685267
• Collaborator: University of Chicago (Other), Astellas Pharma Inc (Industry)
• Enrollment: 9
• Locations: 5
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a prospective randomized phase II clinical trial where patients who are receiving enzalutamide in the pre-chemotherapy space are randomized upon objective progression (radiographic and/or clinical per PCWG2 criteria) to docetaxel/prednisone alone or the same combination plus enzalutamide.

The primary aim is to evaluate whether continuing enzalutamide in combination with docetaxel in patients who failed or progressed while on enzalutamide would increase progression-free survival (PFS) by 4 months. The secondary end points are PSA responses, percent of patients alive at 1 and 2 years, decline in circulating tumor cells (CTCs), and quality of life (QOL) using validated scales.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Docetaxel; Drug: Enzalutamide; Drug: Prednisone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Prospective Trial of Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer (CRPC) Patients Progressing on Enzalutamide
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Docetaxel/Prednisone Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout	Drug: Docetaxel; Drug: Prednisone
Active Comparator: Docetaxel/Prednisone + Enzalutamide Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel.	Drug: Docetaxel; Drug: Enzalutamide; Drug: Prednisone

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (Radiographic or Per PCWG2 Criteria) [1 year]

   The primary endpoint of the study is progression-free survival (PFS), defined as the time from randomization to disease progression. Progression will be evaluated using a combination of RECIST and Prostate Cancer Working Group 2 guidelines.

Secondary Outcome Measures

1. PSA Response in the Standard Treatment Arm and Experimental Treatment Arm [Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231, and every 21 days through study completion (an average of 1 year)]

   PSA response measured according to Prostate Cancer Working Group 2 (PCWG2). The study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm.

2. Overall Survival [At both 1 year and 2 years from treatment start]

Other Outcome Measures

1. Quality of Life (QOL) [Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231 and every 21 days through study completion (an average of 1 year)]

2. Circulating Tumor Cells (CTCs) [Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year)]

3. Analysis of Androgen Receptor Splice Variant [Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.

NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.

• Males 18 years of age and above

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features

• Having documented disease progression on enzalutamide defined by 1 or more of the following criteria:

• PSA progression according to PCWG2 criteria with 3 consecutive rising PSA measurements, all collected at least 1 week apart

• Radiographic progression in soft tissue or bone by modified RECIST 1.1 for subjects with measurable disease; or

• Bone disease progression defined by 2 or more new lesions on 2 consecutive bone scans in the absence of falling PSA

• Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRG-analogue therapy for the duration of the trial

• Serum testosterone level < 50 ng/dL at Screening visit

• ECOG PS: 0-1

• Throughout the study, male patients and their female partners of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration.

Two acceptable methods of birth control thus include the following:

• Condom (barrier method of contraception even if having sex with a pregnant woman)

• One of the following is required:

• Established use of oral, injected, or implanted hormonal method of contraception by the female partner

• Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner

• Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner

• Tubal litigation in the female partner

• Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy) for >6 months

• Patients must have adequate organ and marrow function as defined below

• Leukocytes >3,000/mm3

• absolute neutrophil count >1,500/mm3

• platelets >100,000/mm3

• total bilirubin within normal institutional limits (or <2X the upper limit of normal in those with Gilbert's disease)

• AST(SGOT)/ALT(SGPT) <1.5 X institutional upper limit of normal

• creatinine within normal institutional limits OR

• creatinine clearance* >45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• Estimated life expectancy of > 6 months

• Able to swallow the study drug as prescribed and comply with study requirements

Exclusion Criteria:

• Prior treatment with docetaxel-based chemotherapy

• Prior treatment with abiraterone acetate

• Prior treatment with cabazitaxel

• Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment

• Ongoing investigational treatment

• Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, cardiac disease that would, in the opinion of the investigator, make this protocol unreasonably hazardous

• Major surgery within 4 weeks of enrollment

• Use of an investigational therapeutic agent with 4 weeks of enrollment

• History of seizure or any condition that may predispose to seizure.

• History of loss of consciousness or transient ischemic attack within 12 months of enrollment

• Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease) within last 3 months

• Grade > 2 treatment-related toxicity from prior therapy

• History of hypersensitivity to polysorbate 80

• Any known allergy to the compounds under investigation

• Any other condition which, in the opinion of the Investigator, would preclude participation in this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637
2	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
3	NorthShore University HealthSytem - Kellogg Cancer Center	Evanston	Illinois	United States	60201
4	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
5	Univesity of Wisconsin	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• Prostate Cancer Clinical Trials Consortium
• University of Chicago
• Astellas Pharma Inc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 31, 2017

More Information

Publications

None provided.

• Responsible Party: Prostate Cancer Clinical Trials Consortium
• ClinicalTrials.gov Identifier: NCT02685267
• Other Study ID Numbers: c13-126
• First Posted: Feb 18, 2016
• Last Update Posted: Apr 9, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Docetaxel/Prednisone	Docetaxel/Prednisone + Enzalutamide
Arm/Group Description	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout Docetaxel Prednisone	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel. Docetaxel Enzalutamide Prednisone
Period Title: Overall Study
STARTED	5	4
COMPLETED	5	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Docetaxel/Prednisone	Docetaxel/Prednisone + Enzalutamide	Total
Arm/Group Description	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout Docetaxel Prednisone	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel. Docetaxel Enzalutamide Prednisone	Total of all reporting groups
Overall Participants	5	4	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 40%	2 50%	4 44.4%
>=65 years	3 60%	2 50%	5 55.6%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	68.2	67.25	67.78
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	5 100%	4 100%	9 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 40%	2 50%	4 44.4%
White	3 60%	2 50%	5 55.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	4 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (Radiographic or Per PCWG2 Criteria)
Description	The primary endpoint of the study is progression-free survival (PFS), defined as the time from randomization to disease progression. Progression will be evaluated using a combination of RECIST and Prostate Cancer Working Group 2 guidelines.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

As the study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm, the study was not evaluable for any efficacy endpoints. Sufficient data for the primary endpoint were not collected to provide outcome measures data tables below.

Arm/Group Title	Docetaxel/Prednisone	Docetaxel/Prednisone + Enzalutamide
Arm/Group Description	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout Docetaxel Prednisone	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel. Docetaxel Enzalutamide Prednisone
Measure Participants	5	4
Count of Participants [Participants]	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel/Prednisone
	Comments	The study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm.
	Type of Statistical Test	Other
	Comments	The study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm.
Statistical Test of Hypothesis	p-Value	0.6761
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	log-rank test
	Estimated Value	0.6761
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	PSA Response in the Standard Treatment Arm and Experimental Treatment Arm
Description	PSA response measured according to Prostate Cancer Working Group 2 (PCWG2). The study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm.
Time Frame	Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231, and every 21 days through study completion (an average of 1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel/Prednisone	Docetaxel/Prednisone + Enzalutamide
Arm/Group Description	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout Docetaxel Prednisone	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel. Docetaxel Enzalutamide Prednisone
Measure Participants	5	4
Count of Participants [Participants]	2 40%	3 75%

3. Secondary Outcome

Title	Overall Survival
Time Frame	At both 1 year and 2 years from treatment start

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel/Prednisone	Docetaxel/Prednisone + Enzalutamide
Arm/Group Description	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout Docetaxel Prednisone	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel. Docetaxel Enzalutamide Prednisone
Measure Participants	5	4
Count of Participants [Participants]	2 40%	4 100%

4. Other Pre-specified Outcome

Title	Quality of Life (QOL)
Time Frame	Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231 and every 21 days through study completion (an average of 1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Circulating Tumor Cells (CTCs)
Time Frame	Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Analysis of Androgen Receptor Splice Variant
Time Frame	Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From treatment administration through 30 days after date of last dose
Arm/Group Title	Docetaxel/Prednisone		Docetaxel/Prednisone + Enzalutamide
Arm/Group Description	Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout Docetaxel Prednisone		Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel. Docetaxel Enzalutamide Prednisone
All Cause Mortality
	Docetaxel/Prednisone		Docetaxel/Prednisone + Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		0/4 (0%)
Serious Adverse Events
	Docetaxel/Prednisone		Docetaxel/Prednisone + Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/4 (0%)
Cardiac disorders
Atrial fibrillation	1/5 (20%)	1	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	1/5 (20%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Docetaxel/Prednisone		Docetaxel/Prednisone + Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Anemia	1/5 (20%)		2/4 (50%)
Edema limbs	1/5 (20%)		0/4 (0%)
White blood cell decreased	1/5 (20%)		0/4 (0%)
Neutrophil count decreased	1/5 (20%)		0/4 (0%)
Cardiac disorders
Atrial fibrillation	1/5 (20%)		0/4 (0%)
Eye disorders
Watering eyes	1/5 (20%)		0/4 (0%)
Dry eye	0/5 (0%)		1/4 (25%)
Eye infection	0/5 (0%)		1/4 (25%)
Lacrimation	0/5 (0%)		1/4 (25%)
Gastrointestinal disorders
Nausea	4/5 (80%)		2/4 (50%)
Vomiting	3/5 (60%)		1/4 (25%)
Diarrhea	1/5 (20%)		1/4 (25%)
Constipation	1/5 (20%)		1/4 (25%)
Gastroesophageal reflux disease	1/5 (20%)		0/4 (0%)
Abdominal pain	1/5 (20%)		0/4 (0%)
Mucositis oral	1/5 (20%)		0/4 (0%)
General disorders
Fatigue	5/5 (100%)		4/4 (100%)
Edema limbs	1/5 (20%)		0/4 (0%)
Infections and infestations
Upper respiratory infection	1/5 (20%)		0/4 (0%)
Metabolism and nutrition disorders
Anorexia	4/5 (80%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	2/5 (40%)		0/4 (0%)
Back pain	1/5 (20%)		1/4 (25%)
Muscle weakness lower limb	1/5 (20%)		0/4 (0%)
Generalized muscle weakness	1/5 (20%)		0/4 (0%)
Nervous system disorders
Peripheral sensory neuropathy	2/5 (40%)		2/4 (50%)
Peripheral motor neuropathy	2/5 (40%)		1/4 (25%)
Dizziness	1/5 (20%)		0/4 (0%)
Headache	1/5 (20%)		0/4 (0%)
Bell's Palsy	0/5 (0%)		1/4 (25%)
Psychiatric disorders
Depression	0/5 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)		0/4 (0%)
Sore throat	1/5 (20%)		0/4 (0%)
Nasal congestion	1/5 (20%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Alopecia	3/5 (60%)		3/4 (75%)
Nail discoloration	1/5 (20%)		1/4 (25%)
Dry skin	1/5 (20%)		0/4 (0%)
Left great toe pain	1/5 (20%)		0/4 (0%)
Skin and subcutaneous tissue disorders - Other, specify	1/5 (20%)		0/4 (0%)
Nail loss	0/5 (0%)		1/4 (25%)
Skin irritation	0/5 (0%)		1/4 (25%)
Nail pain	0/5 (0%)		1/4 (25%)
Vascular disorders
Hypotension	1/5 (20%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.