A Phase 1 Study of Crizotinib in Combination With Enzalutamide in Metastatic Castration-resistant Prostate Cancer Before or After Progression on Docetaxel.
Overview
- Phase
- Phase 1
- Intervention
- Crizotinib
- Conditions
- Castration-resistant Prostate Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Rate of dose limiting toxicity (DLT)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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).
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.
Investigators
Christopher Sweeney, MBBS
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
crizotinib and enzalutamide
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
Intervention: Crizotinib
crizotinib and enzalutamide
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
Intervention: Enzalutamide
Outcomes
Primary Outcomes
Rate of dose limiting toxicity (DLT)
Time Frame: 28 Days
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.
Secondary Outcomes
- 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)