Docetaxel or Cabazitaxel with Clarithromycin in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Status: Administratively Complete

Description

This phase Ib trial studies the side effects and best dose of docetaxel or cabazitaxel when given together with clarithromycin in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Drugs used in chemotherapy, such as docetaxel and cabazitaxel, 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. Clarithromycin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel or cabazitaxel with clarithromycin may work better in treating patients with castration-resistant prostate cancer.

Eligibility Criteria

Inclusion Criteria

  • Men with metastatic castrate-resistant prostate cancer (prostate cancer progressing despite castrate levels of testosterone [< 50 ng/dL]), using standard measures of progression defined by Prostate Cancer Working Group 2 (PCWG2)
  • Have received at least 4 cycles of docetaxel or cabazitaxel, and less than ten, with two consecutive rising PSA values, checked at least 7 days apart
  • Radiographic progressive disease, irrespective of PSA changes, after receiving at least 4 cycles of docetaxel or cabazitaxel
  • Bone disease documented by either: a positive bone scan, computed tomography (CT) scan, or magnetic resonance imaging (MRI); or biopsy proven bony metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Docetaxel: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN) (or =< 1.5 x ULN in conjunction with alkaline phosphatase (alk phos) > 2.5 x ULN
  • Cabazitaxel: AST =< 1.5 x ULN
  • Docetaxel: Creatinine clearance no minimum
  • Cabazitaxel: Creatinine clearance >= 30 mL/min/1.73 m^2
  • No evidence of clinical progression, in the form of increased lesions on cross-sectional imaging, or new cancer-attributable symptoms or worsening of existing symptoms
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients who have residual toxicities > grade 2 attributed to taxane therapy, except for neuropathy, who are excluded if > grade 1
  • Patients who are receiving any other investigational agents or have within the last 28 days
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to clarithromycin or taxanes
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible; the subject requires concomitant treatment with the following inhibitors of CYP3A4: * Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin; specifically, clarithryomycin is permitted for patients considered for this trial * Antifungals: itraconzaole, ketoconazole, voriconazole, fluconazole, posaconazole * Antidepressants: nefazodone * Antidiuretic: conivaptan * Antiretrovirals: delaviridine or protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir, nelfinavir) or cobicistat-boosted antiretrovirals * Gastrointestinal (GI): cimetidine, aprepitant * Hepatitis C: boceprevir, telaprevir * Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids)
  • 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
  • Received more than 10 cycles of docetaxel (for docetaxel cohort only) or 6 of cabazitaxel (for cabazitaxel cohort only)
  • Last docetaxel or cabazitaxel dose > 6 weeks prior to enrollment
  • Patients with a documented history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes, or taking drugs that are known to prolong the QT

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Define the safety and tolerability of docetaxel or cabazitaxel in combination with clarithromycin.

II. Determine the maximum tolerated dose and recommended phase 2 dose of docetaxel and of cabazitaxel when it is combined with clarithromycin.

SECONDARY OBJECTIVES:

I. Compare docetaxel OR cabazitaxel exposure (maximal [Cmax] and total [area under curve (AUC)]) when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.

II. To investigate anti-tumor activity of the strategy.

III. To assess the ability of CYP3A4 inhibition to alter both the systemic (secondary objective I) and microenvironmental exposure to chemotherapy.

OUTLINE: This is a dose-escalation study of docetaxel and cabazitaxel. Patients are assigned to 1 of 2 groups.

GROUP I: Patients receive clarithromycin orally (PO) twice daily (BID) on days -1 to 2 and docetaxel intravenously (IV) over 1 hour on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive clarithromycin PO BID on days -1 to 2 and cabazitaxel IV over 1 hour on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Michael Anthony Carducci

Trial IDs

Primary ID J16144
Secondary IDs NCI-2017-01675, IRB00117591, CRMS-65335
Clinicaltrials.gov ID NCT03043989