Crizotinib in Combination With Enzalutamide in Metastatic Castration-resistant Prostate Cancer

NCT02207504 | Completed Phase 1 DMC

• 1 other identifier: 14-230
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is comparing the combination of drugs Crizotinib and Enzalutamide as a possible treatment for metastatic castration-resistant prostate cancer (mCRPC).

Conditions

Castration-resistant Prostate Cancer

Keywords

Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of dose limiting toxicity (DLT)

  Rate of dose limiting toxicity (DLT) in the first 28 days of study therapy by dose level when escalating doses of crizotinib are combined with enzalutamide and when appropriate a GnRH agonist.

  28 Days

Secondary Outcomes (2)

• Pharmacokinetics profiles of crizotinib and enzalutamide when used in combination

  C1D1, C2D1: baseline, 0.5, 1, 2, 4, 6, and 8 hours after dose; prior to dose on C1D2, C2D2, C1D15, C2D15 , C3D1

• The number of patients who experience adverse events and laboratory abnormalities

  2 Years

Other Outcomes (7)

• Time to radiologic disease progression

  2 years

• Blood markers of bone turnover and changes in bone microenvironment

  2 years

• Change in quantity and gene expression of CTCs

  2 years

Study Arms (1)

crizotinib and enzalutamide

EXPERIMENTAL

A traditional 3+3 dose escalation scheme will be used to identify the recommended phase 2 dose (RP2D) of crizotinib when used in combination with standard fixed dose enzalutamide. * Crizotinib- given orally daily-28 day cycle * Enzalutamide- given orally daily-28 day cycle

Drug: Crizotinib; Drug: Enzalutamide

Interventions

Crizotinib DRUG

Crizotinib is an ATP-competitive small-molecule inhibitor of the ALK, c-Met/HGFR, RON, and ROS receptor tyrosine kinases.

Also known as: Xalkori, PF-02341066

crizotinib and enzalutamide

Enzalutamide DRUG

Enzalutamide is an androgen receptor signaling inhibitor.

Also known as: XTANDI, MDV3100

crizotinib and enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Laboratory and diagnostic tests, such as MRIs and CT scans, required for eligibility must be documented from tests performed within 30 days prior to the date of registration.
• The patient has pathologically confirmed adenocarcinoma of the prostate
• The subject must have CRPC with castrate levels of serum testosterone less than 50 ng/dL.
• \-- NOTE: Subjects must maintain a castrate state. If they have not had an orchiectomy must continue to receive LHRH or GnRH agonists unless intolerant.
• Evidence of metastatic disease by radiographic imaging (bone scan or other nodal or visceral lesions on CT or MRI)
• Prostate cancer progression since last prior therapy documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria Version 1.1
• No limit on number or type of prior therapies
• Prior treatment with docetaxel is permitted but not required
• Prior treatment with ketoconazole, estrogens, abiraterone or novel antiandrogens allowed, including past enzalutamide
• Require at least a 6 week withdrawal period from the last dose of bicalutamide, or nilutamide or 4 weeks from last flutamide or enzalutamide dose Must have a documented PSA rise after stopping the antiandrogen --- Will require a 2 week washout period from last dose of ketoconazole, chemotherapy, or radiation
• Prior radiation is allowed
• Age ≥18 years
• ECOG performance status \<2 (See Appendix 1)
• Life expectancy of greater than 6 months
• Participants must have normal organ and marrow function as defined below:

You may not qualify if:

• Pathology consistent with small cell carcinoma of the prostate
• Prior treatment with c-Met inhibitors
• Participants who have received any other investigational systemic agents in the last 2 weeks.
• Persistent grade \>1 (NCI CTCAE v4.0) AEs due to investigational drugs that were administered more than 14 days before study enrollment with the exception of alocepia.
• Participants with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction or seizures that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to crizotinib or enzalutamide.
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, history of loss of consciousness or transient ischemic attack within 12 months of study entry).
• Concomitant medications that would lower seizure threshold
• Concomitant use of medications that may alter pharmacokinetics of crizotinib or enzalutamide. See section 5.5, but would exclude the use of strong CYP3A or CYP2C8 inhibitors, strong or moderate CYP3A inducers, CYP2C8, CYP3A4, CYP2C9 and CYP2C19 substrates with narrow therapeutic indice.
• \-- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as: http://medicine.iupui.edu/clinpharm/ddis/table.aspx
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Clinically significant heart disease defined as:
• Myocardial infarction within 6 months of Screening visit.
• Uncontrolled angina within 3 months of Screening visit.
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the Screening visit results in a left ventricular ejection fraction that is ≥45%.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Astellas Pharma Inc: collaborator
• Pfizer: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

Crizotinib; enzalutamide

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Christopher Sweeney, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 4, 2014
• Study Start: August 1, 2014
• Primary Completion: February 2, 2018
• Study Completion: January 3, 2022
• Last Updated: January 6, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)