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Cyclophosphamide and Dexamethasone for the Treatment of Metastatic Castration Resistant Prostate Cancer

Primary Purpose

Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer American Joint Committee on Cancer (AJCC) v8

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Dexamethasone
Sponsored by
Rashmi Verma, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Castration-Resistant Prostate Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to understand and willingness to sign an informed consent form
  • Ability to adhere to the study visit schedule and other protocol requirements
  • Adults >= 18 years of age at time of consent
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
  • Life expectancy >= 3 months
  • Histologically or cytologically confirmed prostate adenocarcinoma
  • Metastatic status defined as at least 1 documented metastatic lesion on a bone scan, a computed tomography (computed tomography [CT] or CT/ positron emission tomography [PET]) scan, or a magnetic resonance imaging (MRI) scan
  • Must have less than 50 ng/dL testosterone
  • Must have demonstrated disease progression after treatment with 2 or more prior lines of therapies for castration resistant prostate cancer (CRPC), including one second generation androgen targeted agent (such as abiraterone or enzalutamide).
  • PSA defined progression after most recent directed therapy. Progression is defined as PSA increase >= 25% of baseline or absolute increase of >= 2 ug/L on two PSA measurements at least 7 days apart
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 8 g/dL
  • Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
  • Aspartate aminotransferase (AST) and alanine transaminase (ALT) levels =< 2.5 × ULN or AST and ALT levels =< 5 x ULN (for participants with documented metastatic disease to the liver)
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (for participants on anticoagulation they must be receiving a stable dose for at least 1 week prior to first treatment)
  • Creatinine clearance > 30 mL/min by Cockcroft-Gault formula
  • Participants with BRCA1/2 or homologous recombination (HR) deoxyribonucleic acid (DNA) repair mutations, and/ or microsatellite instability (MSI) must have received prior treatment (e.g., PARP [poly adenosine diphosphate-ribose polymerase] inhibitors or other agents) for BReast CAncer gene (BRCA)/ homologous recombination (HR) DNA repair mutation and/ or MSI
  • Participants with known active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is < 100 IU/mL prior to first dose of trial treatment. Participants with treated or untreated hepatitis C virus (HCV) are allowed.
  • Male participants who agree to use highly effective method of birth control with their partner (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices [IUDs], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug

Exclusion Criteria:

  • Any condition that would prohibit the understanding or rendering of informed consent
  • A history of any other active malignancy with progression and requiring treatment/intervention, with the exception of cutaneous malignancies such as basal cell carcinoma, squamous cell carcinoma, melanoma, or the type of malignancy being studied in this protocol
  • Participants with urinary outflow obstruction that has not been treated or managed with either indwelling catheter or self-catheterization
  • Severe untreated infection that in the opinion of the investigator would interfere with participant safety or compliance on trial within 28 days prior to enrollment
  • Any condition, including concomitant disease, additional malignancies, laboratory abnormalities, or psychiatric illness, that in the opinion of the investigator would interfere with the participant's safety or compliance while on trial
  • Use of systemic therapy for the treatment of prostate adenocarcinoma within 2 weeks of initiating study treatment

Sites / Locations

  • University of California Davis Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cyclophosphamide, dexamethasone)

Arm Description

Patients receive cyclophosphamide PO QD and dexamethasone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Feasibility
Feasibility, defined as >= 80% of participants completing treatment, and safety as defined by Grade 3 or higher adverse events (AEs) observed per National Cancer Institute (NCI) Common Terminology Criteriafor Adverse Events (CTCAE 5.0) criteria
Incidence of adverse events
Number of participants experiencing adverse events (AEs), both non treatment related and treatment related, classified by severity and graded.

Secondary Outcome Measures

Total prostate-specific antigen (PSA) response rate
Defined as a decline in PSA of 50% or greater, confirmed evaluation every 28 days with no evidence of clinical progression or disease progression on imaging, consistent with previous definitions by the Prostate Cancer Working Group 2 (PCWG2). The PSA response rate will be estimated along with an exact 95% confidence interval. Kaplan-Meier analysis will be used to depict time-to-event outcomes graphically and estimate medians with 95% confidence intervals.
Time to no longer clinical benefit (NLCB)
Time to prostate-specific antigen (PSA) progression
Time to radiographic progression free survival (rPFS)

Full Information

First Posted
July 18, 2022
Last Updated
October 8, 2022
Sponsor
Rashmi Verma, MD
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05479578
Brief Title
Cyclophosphamide and Dexamethasone for the Treatment of Metastatic Castration Resistant Prostate Cancer
Official Title
A Phase I Study of Oral Metronomic Dosing of Oral Cyclophosphamide With Dexamethasone for Metastatic Castration Resistant Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 29, 2022 (Actual)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Rashmi Verma, MD
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I trial tests the safety and side effects of cyclophosphamide given together with dexamethasone in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving low doses of cyclophosphamide daily may reduce side effects. Dexamethasone is a corticosteroid drug that is used to treat some of the problems caused by chemotherapy treatment. The combination of cyclophosphamide and dexamethasone may work better in treating patients with castration resistant prostate cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the feasibility of using the combination of oral metronomic cyclophosphamide and oral dexamethasone for treatment of men with metastatic castration -resistant prostate Cancer (mCRPC) who have progressed on 2 or more prior treatments. II. To assess the safety of cyclophosphamide + dexamethasone in men with mCRPC who have progressed on 2 or more prior treatments. SECONDARY OBJECTIVE:I. To evaluate prostate specific antigen (PSA) response and progression free survival and time to event outcome in participants with mCRPC treated with cyclophosphamide and dexamethasone. EXPLORATORY OBJECTIVE: I. To analyze serial blood samples for PSA monitoring and tumor tissue for pRb (encoded by the RB1 gene) and p53 (encoded by the TP53 gene) mutations. OUTLINE: Patients receive cyclophosphamide orally (PO) once daily (QD) and dexamethasone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer American Joint Committee on Cancer (AJCC) v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cyclophosphamide, dexamethasone)
Arm Type
Experimental
Arm Description
Patients receive cyclophosphamide PO QD and dexamethasone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Feasibility
Description
Feasibility, defined as >= 80% of participants completing treatment, and safety as defined by Grade 3 or higher adverse events (AEs) observed per National Cancer Institute (NCI) Common Terminology Criteriafor Adverse Events (CTCAE 5.0) criteria
Time Frame
Treatment initiation through treatment completion, an average of up to 4 years
Title
Incidence of adverse events
Description
Number of participants experiencing adverse events (AEs), both non treatment related and treatment related, classified by severity and graded.
Time Frame
Treatment initiation through treatment completion, an average of up to 4 years
Secondary Outcome Measure Information:
Title
Total prostate-specific antigen (PSA) response rate
Description
Defined as a decline in PSA of 50% or greater, confirmed evaluation every 28 days with no evidence of clinical progression or disease progression on imaging, consistent with previous definitions by the Prostate Cancer Working Group 2 (PCWG2). The PSA response rate will be estimated along with an exact 95% confidence interval. Kaplan-Meier analysis will be used to depict time-to-event outcomes graphically and estimate medians with 95% confidence intervals.
Time Frame
From date of treatment initiation through PSA response (as defined by Prostate Cancer Working Group 2 [PCWG2]), an average of up to 4 years
Title
Time to no longer clinical benefit (NLCB)
Time Frame
Treatment initiation through treatment completion, an average of up to 4 years
Title
Time to prostate-specific antigen (PSA) progression
Time Frame
From date of treatment initiation to PSA progression (as defined by Prostate Cancer Working Group 2 [PCWG2]), an average of up to 4 years
Title
Time to radiographic progression free survival (rPFS)
Time Frame
From date of treatment initiation to radiographic progression (as defined by Prostate Cancer Working Group 2 [PCWG2]) or date of death from any cause, whichever came first, an average of up to 4 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to understand and willingness to sign an informed consent form Ability to adhere to the study visit schedule and other protocol requirements Adults >= 18 years of age at time of consent Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2 Life expectancy >= 3 months Histologically or cytologically confirmed prostate adenocarcinoma Metastatic status defined as at least 1 documented metastatic lesion on a bone scan, a computed tomography (computed tomography [CT] or CT/ positron emission tomography [PET]) scan, or a magnetic resonance imaging (MRI) scan Must have less than 50 ng/dL testosterone Must have demonstrated disease progression after treatment with 2 or more prior lines of therapies for castration resistant prostate cancer (CRPC), including one second generation androgen targeted agent (such as abiraterone or enzalutamide). PSA defined progression after most recent directed therapy. Progression is defined as PSA increase >= 25% of baseline or absolute increase of >= 2 ug/L on two PSA measurements at least 7 days apart Absolute neutrophil count (ANC) >= 1.0 x 10^9/L Platelet count >= 100 x 10^9/L Hemoglobin >= 8 g/dL Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range Aspartate aminotransferase (AST) and alanine transaminase (ALT) levels =< 2.5 × ULN or AST and ALT levels =< 5 x ULN (for participants with documented metastatic disease to the liver) International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (for participants on anticoagulation they must be receiving a stable dose for at least 1 week prior to first treatment) Creatinine clearance > 30 mL/min by Cockcroft-Gault formula Participants with BRCA1/2 or homologous recombination (HR) deoxyribonucleic acid (DNA) repair mutations, and/ or microsatellite instability (MSI) must have received prior treatment (e.g., PARP [poly adenosine diphosphate-ribose polymerase] inhibitors or other agents) for BReast CAncer gene (BRCA)/ homologous recombination (HR) DNA repair mutation and/ or MSI Participants with known active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is < 100 IU/mL prior to first dose of trial treatment. Participants with treated or untreated hepatitis C virus (HCV) are allowed. Male participants who agree to use highly effective method of birth control with their partner (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices [IUDs], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug Exclusion Criteria: Any condition that would prohibit the understanding or rendering of informed consent A history of any other active malignancy with progression and requiring treatment/intervention, with the exception of cutaneous malignancies such as basal cell carcinoma, squamous cell carcinoma, melanoma, or the type of malignancy being studied in this protocol Participants with urinary outflow obstruction that has not been treated or managed with either indwelling catheter or self-catheterization Severe untreated infection that in the opinion of the investigator would interfere with participant safety or compliance on trial within 28 days prior to enrollment Any condition, including concomitant disease, additional malignancies, laboratory abnormalities, or psychiatric illness, that in the opinion of the investigator would interfere with the participant's safety or compliance while on trial Use of systemic therapy for the treatment of prostate adenocarcinoma within 2 weeks of initiating study treatment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Selina Laqui
Phone
916-734-0565
Email
sblaqui@ucdavis.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rashmi Verma, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Selina Laqui
Phone
916-734-0565
Email
sblaqui@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Rashmi Verma, MD

12. IPD Sharing Statement

Learn more about this trial

Cyclophosphamide and Dexamethasone for the Treatment of Metastatic Castration Resistant Prostate Cancer

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