Toxicity & Pharmacokinetics of 2 & 3-weekly Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

NCT03343977 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: MCC-17-GU-71
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to investigate the toxicity and pharmacokinetics (PK) of 2-weekly and 3-weekly docetaxel in metastatic hormone-sensitive prostate cancer (mHSPC). Also, a mechanism-based population pharmacokinetics/pharmacodynamics (PK/PD) model will be developed to provide a better understanding of the complex relationships between the drug exposure and toxicity profiles of docetaxel in mHSPC.

Conditions

Metastatic Hormone-Sensitive Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Comparison of the neutropenia toxicity rate over time between the 2-weekly docetaxel dosing regimen and the 3-weekly docetaxel dosing regimen in metastatic hormone-sensitive prostate cancer.

  Toxicity rate in each arm will be estimated based on a one-sided 90% confidence interval. Assuming at most a 31% neutropenia rate, a sample of 16 patients per arm will provide a one-sided 90% confidence interval upper limit equal to 50%.

  Baseline; at each therapy cycle (a cycle is 2 weeks for the 2-weekly regimen, 3 weeks for the 3-weekly regimen); at 6-, 9-, and 12-months post treatment

Secondary Outcomes (10)

• Comparison of the pharmacokinetics (PK) parameter 'Cmax' (maximum concentration) between the 2-weekly docetaxel dosing regimen and the 3-weekly docetaxel dosing regimen in metastatic hormone-sensitive prostate cancer.

  0, 0.25, 0.75, 3, 6.5, and 24 hours post first docetaxel infusion; and, at the end of docetaxel infusion of the last cycle (a cycle is 2 weeks for the 2-weekly regimen, 3 weeks for the 3-weekly regimen)

• Comparison of the pharmacokinetics (PK) parameter 'Tmax' (time to Cmax) between the 2-weekly docetaxel dosing regimen and the 3-weekly docetaxel dosing regimen in metastatic hormone-sensitive prostate cancer.

  0, 0.25, 0.75, 3, 6.5, and 24 hours post first docetaxel infusion; and, at the end of docetaxel infusion of the last cycle (a cycle is 2 weeks for the 2-weekly regimen, 3 weeks for the 3-weekly regimen)

• Comparison of the pharmacokinetics (PK) parameter 'AUClast' between the 2-weekly docetaxel dosing regimen and the 3-weekly docetaxel dosing regimen in metastatic hormone-sensitive prostate cancer.

  0, 0.25, 0.75, 3, 6.5, and 24 hours post first docetaxel infusion; and, at the end of docetaxel infusion of the last cycle (a cycle is 2 weeks for the 2-weekly regimen, 3 weeks for the 3-weekly regimen)

• Comparison of the pharmacokinetics (PK) parameter 't1/2' (terminal half-life) between the 2-weekly docetaxel dosing regimen and the 3-weekly docetaxel dosing regimen in metastatic hormone-sensitive prostate cancer.

  0, 0.25, 0.75, 3, 6.5, and 24 hours post first docetaxel infusion; and, at the end of docetaxel infusion of the last cycle (a cycle is 2 weeks for the 2-weekly regimen, 3 weeks for the 3-weekly regimen)

• Comparison of the pharmacokinetics (PK) parameter 'AUC0-inf' (area under the curve from zero to infinity)' between the 2-weekly docetaxel dosing regimen and the 3-weekly docetaxel dosing regimen in metastatic hormone-sensitive prostate cancer.

  0, 0.25, 0.75, 3, 6.5, and 24 hours post first docetaxel infusion; and, at the end of docetaxel infusion of the last cycle (a cycle is 2 weeks for the 2-weekly regimen, 3 weeks for the 3-weekly regimen)

Study Arms (2)

Every two weeks docetaxel

EXPERIMENTAL

50 mg/m2 of docetaxel will be given on day 1 every 14 days over one hour IV infusion for up to 9 cycles (1 cycle = 14 days)

Drug: docetaxel 50mg/m2

Every three weeks docetaxel

ACTIVE COMPARATOR

75 mg/m2 of docetaxel will be given on day 1 every 21 days over one hour IV infusion for up to 6 cycles (1 cycle = 21 days)

Drug: docetaxel 75mg/m2

Interventions

docetaxel 50mg/m2 DRUG

50 mg/m2 of docetaxel will be given on day 1 every 14 days

Every two weeks docetaxel

docetaxel 75mg/m2 DRUG

75 mg/m2 of docetaxel will be given on day 1 every 21 days

Every three weeks docetaxel

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed prostate cancer with EXTENSIVE metastatic disease and have been on androgen deprivation therapy for \<90 days. Hormonal therapy must not have commenced more than 90 days prior to study.
• Definition of extensive disease: Metastases involving at least one lesion in any bony structures beyond the vertebral column and pelvic bone or any involvement with viscera. In the absence of visceral lesion, there must be four or more bone lesions. Patients with disease limited to vertebral column and/or pelvis alone with or without lymph node or lymph node only disease involvement are not eligible for this trial.
• Age ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%).
• Patients must have normal organ and marrow function as defined below within four weeks prior to the study:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin less than ULN
• AST(SGOT)/ALT(SGPT) ≤1.5 × institutional upper limit of normal
• Alkaline phosphate ≤2.5 x ULN
• Creatinine clearance ≥ 30 mL/min calculated using the Cockcroft-Gault formula: Creatinine clearance for male (mL/min) = (140-age)\*(body weight in kg)/(72 x serum creatinine in mg/dl)
• If a patient has had major surgery, the patient must be longer than four weeks post surgery and must have recovered from all toxicity prior to beginning protocol study.
• Peripheral neuropathy with Grade ≤1
• Patients may be enrolled if they have had prior palliative radiation therapy. However, this has to have been commenced within 30 days of starting androgen deprivation.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of hypersensitivity to docetaxel or polysorbate 80.
• 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 dysfunction that could impair the ability of the patients to participate in the study or interfere with interpretation of study results.
• Docetaxel is a CYP3A4 substrate and caution should be taken with its use and any drugs known to interact with it. 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; medical reference texts such as the Physicians' Desk Reference for this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Appendix B contains a list of known drugs that are contraindicated or have major interactions with docetaxel.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with docetaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Patients with prior docetaxel chemotherapy.

Sponsors & Collaborators

• Peng Wang, MD PhD: lead

Study Sites (1)

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Interventions

Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Peng Wang, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: November 17, 2017
• Study Start: February 14, 2018
• Primary Completion: April 30, 2019
• Study Completion (Estimated): April 30, 2029
• Last Updated: July 17, 2018

Record last verified: 2018-06

Locations

US (1)