Trial Outcomes & Findings for Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment (NCT NCT02047253)

NCT ID: NCT02047253

Last Updated: 2018-12-19

Results Overview

The study will measure patient survival at 6 months but will continue to monitor overall survival as a secondary objective. The Kaplan-Meier method will be used.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: Baseline through 6 months for evaluating all patients
• Results posted on: 2018-12-19

Participant Flow

Protocol Open to Accrual: April 2014, Primary Completion Date: June 2017 and Study Completion Date: July 14, 2017. Recruitment location: University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham; Tulane University, New Orleans; Medical Center of Central Georgia, Macon, Georgia, Dana Farber Cancer Institute, Boston.

Participant milestones

Measure	Carfilzomib Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily
Overall Study STARTED	28
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure

Carfilzomib Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily

Overall Study Lost to Follow-up

8

Baseline Characteristics

Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment

Baseline characteristics by cohort

Measure	Carfilzomib n=28 Participants Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=93 Participants
Age, Categorical >=65 years	15 Participants n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	28 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants
Race (NIH/OMB) White	22 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	28 participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline through 6 months for evaluating all patients

Population: 8 patients did not complete treatment and were not included in the analysis.

The study will measure patient survival at 6 months but will continue to monitor overall survival as a secondary objective. The Kaplan-Meier method will be used.

Outcome measures

Measure

Carfilzomib n=20 Participants Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily

Progression-free Survival (PFS)

1 Participants

PRIMARY outcome

Timeframe: From baseline through 36 months.

Population: 8 patients did not complete treatment and were lost to follow up

Outcome measure was completed by using a count of participants.

Outcome measures

Measure

Carfilzomib n=20 Participants Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily

Overall Survival

11 Participants

SECONDARY outcome

Timeframe: Baseline through 36 months

Population: We were unable to collect blood specimen for PSA analysis for 1 patient.

PSA levels were collected at each visit on the day of treatment. Linear regression with PSA as the dependent variable and time as the dependent variable was performed.

Outcome measures

Measure

Carfilzomib n=27 Participants Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily

Number of Participants With Prostate-Specific Antigen (PSA) Changes

3 Participants

SECONDARY outcome

Timeframe: Baseline through 36 months

Population: 1 patient did not have blood draw. 27 patients had blood draws for CTC enumeration across baseline, Cycle 2 day 1 and cycle 4 day 1.

The CTC marker will be used to evaluate efficacy of response to treatment. CTC changes will include changes from unfavorable (less than or equal to 5/7.5 ml) to favorable and declines by >30%.

Three collections: before study initiation, Day 1 of Cycles 2 and 4

Outcome measures

Measure	Carfilzomib n=27 Participants Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily
Number of Participants With Circulating Tumor Cell (CTC) Decline Over Three Time Points (Before Study Initiation, Day 1 of Cycles 2 and 4 CTC decline	3 Participants
Number of Participants With Circulating Tumor Cell (CTC) Decline Over Three Time Points (Before Study Initiation, Day 1 of Cycles 2 and 4 CTC increased or No change/decline in CTC levels	24 Participants

SECONDARY outcome

Timeframe: Baseline through 36 months

Population: All serious adverse events and \> grade 3 toxicities were reported for patients who received treatment with Carfilzomib

Hematologic and non-hematologic toxicities will be graded. The new international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) will serve as the guideline.

On Day 1 of each cycle (4 weeks) for the duration of treatment and then 30 days following the last treatment

Outcome measures

Measure	Carfilzomib n=28 Participants Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily
Assessment of Toxicities Anemia (>= Grade 3 or 4)	3 Participants
Assessment of Toxicities Hypertension (>= Grade 3 or 4)	2 Participants

Adverse Events

Carfilzomib

Serious events: 5 serious events

Other events: 0 other events

Deaths: 6 deaths

Serious adverse events

Measure	Carfilzomib n=28 participants at risk Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient. Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. Dexamethasone: Administered prior to administration of Study drug Acyclovir: Administered orally twice daily
Blood and lymphatic system disorders Anemia	10.7% 3/28 • Number of events 3 • Adverse event data were collected over 36 months.
Cardiac disorders Hypertension	7.1% 2/28 • Number of events 2 • Adverse event data were collected over 36 months.

Other adverse events

Adverse event data not reported

Additional Information

Pam Dixon, RN, BSN, OCN

University of Alabama at Birmingham

Phone: 205-975-9875

Email: pamdixon@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place