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Castration-resistant Prostate CancerPhase 1NCT02207504

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

A Phase 1 study testing Crizotinib and Enzalutamide in people with Castration-resistant Prostate Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Castration-resistant Prostate Cancer
What is being tested?
Crizotinib and Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
Aug 2014to 3 Jan 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Absolute neutrophil count ≥1,500/mcL
  • Hemoglobin ≥8 g/dL
  • ---Transfusions and erythropoietin supplementation permitted
  • Platelets ≥100,000/mcL
  • Total bilirubin within normal institutional limits (unless known Gilbert's syndrome)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal or ≤5X if presence of liver metastases
  • --- For patients with documented bone metastases, AST can be > 2.5x ULN if the investigator can provide evidence of no underlying liver dysfunction and thus, it is likely that the AST is originating from bone source.
  • Creatinine clearance ≥30 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Able to swallow the study drug as a whole tablet
  • The effects of crizotinib and enzalutamide on the developing human fetus are unknown. For this reason and because investigational agents as well as other standard antiandrogen agents used in this trial may be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of crizotinib administration.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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%.
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes).
  • Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec.
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
  • Hypotension (systolic blood pressure <86 mmHg) or bradycardia with a heart rate of <50 beats per minute on the Screening ECG, unless pharmaceutically induced and thus reversible (i.e. beta blockers) or known, chronic asymptomatic baseline heart rate.
  • Uncontrolled hypertension as indicated by a resting systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg at the Screening visit.
  • No medications known to prolong the QT interval as crizotinib may increase the risk for QT prolongation
  • Thrombosis or vascular ischemic events within the last six months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction
  • No medications known to prolong the QT interval as crizotinib may increase the risk for QT prolongation
  • Pregnant women are excluded from this study because women do not get prostate cancer, as they have no prostate.
  • No defined washout period from major or minor surgery is required but incisions must be fully healed.
  • HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with crizotinib or enzalutamide. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Inability to comply with study and/or follow-up procedures

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 1 Study of Crizotinib in Combination With Enzalutamide in Metastatic Castration-resistant Prostate Cancer Before or After Progression on Docetaxel.

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

Read the detailed description
  • 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.
  • Patients who fulfill eligibility criteria will be entered into the trial to receive crizotinib and enzalutamide.
  • After the screening procedures confirm participation in the research study:
  • The participant will be given a study drug-dosing calendar for each treatment cycle. The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.
Being tested
Crizotinib, Enzalutamide
Keywords
Castration-resistant Prostate Cancer

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CrizotinibDrug

    Also called Xalkori, PF-02341066

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

  • EnzalutamideDrug

    Also called XTANDI, MDV3100

    Enzalutamide is an androgen receptor signaling inhibitor.

Study groups in NCT02207504
Study groupRoleWhat they receive
crizotinib and enzalutamideExperimentalA 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
Receives: Drug: Crizotinib; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 28 Days

Secondary outcomes (2)

  1. Pharmacokinetics profiles of crizotinib and enzalutamide when used in combination

    Pharmacokinetic parameters will be determined using noncompartmental methods with WinNonLin version 5.2. Maximum blood concentration (Cmax) and time of maximum blood concentration (tmax) will be determined by visual inspection. The area under the blood concentration-time curve (linear trapezoidal rule) will be determined between 0-24 hours (AUC0-24)/. The mean (+/- STDEM) concentration-time profiles of both crizotinib and enzalutamide will be presented for each dose.

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

  2. The number of patients who experience adverse events and laboratory abnormalities

    The tolerability of the combination as defined as toxicity that results in study drug discontinuation or dose reduction that would not have been mandated by the protocol such as a DLT

    Measured: 2 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2014 (estimated)
  2. Study startAug 2014
  3. Primary completion2 Feb 2018
  4. Study completion3 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02207504
Sponsor's protocol ID
14-230
Status last verified
Jan 2022
First submitted
30 Jul 2014
Last updated
6 Jan 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Crizotinib and Enzalutamide in people with Castration-resistant Prostate Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of dose limiting toxicity (DLT) (time frame: 28 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02207504.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2022.

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