Conventional Prophylactic Oral Dexamethasone vs Short-course IV Dexamethasone in Paclitaxel Hypersensitivity

Conventional Prophylactic Regimen of Oral Dexamethasone Versus Short-course Intravenous Dexamethasone in Preventing Paclitaxel-related Hypersensitivity Reactions in Breast and Gynecologic Oncology Patients

This study is a single center, prospective, randomized, open-label study aimed at determining the most effective means of preventing hypersensitivity reactions in gynecologic oncology patients receiving paclitaxel infusions. The study will therefore provide clinicians with the best ways of preventing paclitaxel hypersensitivity reactions in their patients during treatment. Subjects will be randomized using the block randomization method into one of these three commonly used treatment methods:(1) Conventional method: oral dexamethasone (20 mg), taking 12 hours and 6 hours prior to paclitaxel infusion and intravenous administration of histamine-1 (H1), and a histamine-2 (H2)receptor antagonists administered 30 minutes prior to paclitaxel infusion. (2) Short-course method: intravenous dexamethasone (20 mg), administered concurrently with H1 and H2 antagonists, 30 minutes prior to paclitaxel infusion. (3) Combined method: oral dexamethasone (20 mg), taking 12 hours prior to treatment in addition to intravenous dexamethasone (20 mg), H1 and H2 receptor antagonists administered 30 minutes prior to paclitaxel infusion. The one-way analysis of variance (ANOVA) would be used to determine if there is any significant difference between the different strategies that are used to pre-medicate patients prior to paclitaxel infusion. P-values of less than 0.05 will be considered statistically significant.

Study Overview

• Status: Recruiting
• Conditions: Hypersensitivity Reactions
• Intervention / Treatment: Drug: Dexamethasone

Detailed Description

One of the potentially serious and dose-limiting toxicities of paclitaxel is the development of hypersensitivity reactions (HSRs). Up to 42% of patients receiving paclitaxel experience an HSR, with serious (> grade 3) reactions observed in about 2% of patients. Paclitaxel prescribing information and many other references therefore strongly recommend pre-medicating patients who are to be treated with paclitaxel-containing regimen with a corticosteroid, a histamine-1 (H1), and a histamine-2 (H2) antagonist prior to paclitaxel infusion. This is done to help prevent or minimize the occurrence of HSRs that could be caused by treating patients with paclitaxel. However, the method and timing of administering these pre-medications (particularly in the case of dexamethasone) have not been standardized. The current and most commonly used methods of preventing paclitaxel HSR includes one of the following: 1. Administering oral dexamethasone (20 mg), 12 hours and 6 hours prior to paclitaxel infusion and intravenous administration of H1 and H2 receptor antagonists 30 minutes prior to paclitaxel infusion (Conventional method); 2. Administering intravenous dexamethasone (20 mg), concurrently with H1 and H2 antagonists, 30 minutes prior to paclitaxel infusion (Short-course method); 3. Administering oral dexamethasone (20 mg), 12 hours prior to treatment in addition to intravenous dexamethasone (20 mg), H1 and H2 receptor antagonists administered 30 minutes prior to paclitaxel infusion. The goal of this study is to do a single center, prospective, randomized, open-label study to determine the most effective method in preventing paclitaxel HSR among these three commonly used methods.

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kofi Donkor, PharmD; Phone Number: 15039 909-558-4000; Email: kndonkor@llu.edu
• Study Contact Backup: Name: Linda Hong, MD; Phone Number: 15504 909-558-4000; Email: lihong@llu.edu

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University Cancer Center
      • Contact: Kofi Donkor, PharmD; Phone Number: 15039 909-558-4000; Email: kndonkor@llu.edu
      • Contact: Linda Hong, MD; Phone Number: 15504 909-558-4000; Email: lihong@llu.edu
      • Sub-Investigator: Julie Selim, PharmD
      • Sub-Investigator: Yevgeniya Ioffe, MD
      • Sub-Investigator: Mazdak Momeni, MD
      • Sub-Investigator: Kofi Donkor, PharmD
      • Sub-Investigator: Gayathri Nagaraj, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult female patients > 18 years of age
2. Patients of the Loma Linda University Health (LLUH) gynecologic oncology and breast oncology service
3. Confirmed breast or gynecologic cancer diagnosis of any stage and any gynecologic or breast malignancy
4. Planned treatment with paclitaxel containing regimen either in the adjuvant setting or for palliation
5. Planned treatment with paclitaxel should be for 3 or more cycles given as a weekly or every 3 weeks cycle

6. Paclitaxel should be given as a monotherapy or as part of a combination regimen. If paclitaxel is part of a regimen containing other drugs, the following conditions must be met:

   1. Paclitaxel will be the first chemotherapy regimen to be infused when patient comes in for treatment
   2. Chemotherapy regimen that would be approved for the study are the following:

   i. Paclitaxel/ Carboplatin ii. Paclitaxel/Carboplatin/Bevacizumab iii. Paclitaxel/Cisplatin/Bevacizumab iv. Paclitaxel/Bevacizumab v. Paclitaxel/ Ifosfamide vi. Paclitaxel/ Pazopanib

7. Patients should have no prior exposure to taxanes (this includes: paclitaxel, docetaxel, and protein-bound paclitaxel)
8. The chemotherapy treatment should be at one of the LLUH Adult Cancer Centers
9. The patient should be an English or Spanish speaking patient

Exclusion Criteria:

1. Patients who are not with the gynecologic or breast oncology service
2. Patients who are with the gynecologic oncology or breast oncology service but are not receiving paclitaxel either as a monotherapy or in combination with other regimen
3. Patients who have had prior exposure to taxanes (this includes: paclitaxel, docetaxel, and protein-bound paclitaxel)
4. Patients who are currently on steroid therapy and it is anticipated that therapy will not be discontinued at least a week prior to start of chemotherapy

5. Patients with autoimmune diseases, malignancies, and any other co-morbid condition that might require steroid therapy during chemotherapy. This includes, but not limited to:

   1. Crohn's disease
   2. Immune thrombocytopenia
   3. Lupus nephritis
   4. Multiple sclerosis
   5. Primary brain tumors
   6. Multiple Myeloma
   7. Hodgkin's Lymphoma
6. Patients with uncontrolled diabetes or diabetic or pre-diabetic patients with baseline A1C levels > 8.5
7. Patients who are allergic to diphenhydramine and/or dexamethasone
8. Non-English and Non-Spanish speaking patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional; Oral dexamethasone (20 mg) at home, 12 hours and 6 hours prior to paclitaxel infusion. On the day of treatment at the clinic, an intravenous administration of diphenhydramine 50 mg and famotidine 20 mg, administered 30 minutes prior to paclitaxel infusion.	Drug: Dexamethasone; Conventional arm will only use oral dexamethasone as intervention; Short-Course arm will only use intravenous dexamethasone as intervention; Combined arm will use both oral and intravenous dexamethasone as intervention; Other Names: Decadron
Active Comparator: Short-Course; Intravenous administration of dexamethasone 20 mg, along with an intravenous administration of diphenhydramine 50 mg and famotidine 20 mg, administered 30 minutes prior to paclitaxel infusion.	Drug: Dexamethasone; Conventional arm will only use oral dexamethasone as intervention; Short-Course arm will only use intravenous dexamethasone as intervention; Combined arm will use both oral and intravenous dexamethasone as intervention; Other Names: Decadron
Active Comparator: Combined; Oral dexamethasone (20 mg) at home, 12 hours prior to paclitaxel infusion. On the day of treatment at the clinic, an additional intravenous administration of dexamethasone 20 mg, along with an intravenous administration of diphenhydramine 50 mg and famotidine 20 mg, administered 30 minutes prior to paclitaxel infusion.	Drug: Dexamethasone; Conventional arm will only use oral dexamethasone as intervention; Short-Course arm will only use intravenous dexamethasone as intervention; Combined arm will use both oral and intravenous dexamethasone as intervention; Other Names: Decadron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least incidence of any-grade-paclitaxel-HSR first cycle	The treatment group that had the least incidence of any-grade-paclitaxel-HSR in the first cycle of chemotherapy treatment	1 to 3 HOURS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least incidence of any-grade-paclitaxel-HSR in the first and second cycles	The treatment group that had the least incidence of any-grade-paclitaxel-HSR in the first and second cycles of chemotherapy treatment	1 to 3 HOURS
Least incidence of grade 3 or more paclitaxel-HSR in the first and second cycles	The treatment group that had the least incidence of grade 3 or more paclitaxel-HSR in the first and second cycles of chemotherapy treatment	1 to 3 HOURS
Least incidence of any-grade-paclitaxel-HSR second cycle	The treatment group that had the least incidence of any-grade-paclitaxel-HSR in the second cycle of chemotherapy treatment	1 to 3 HOURS
Least incidence of grade 3 or more paclitaxel-HSR first cycle	The treatment group that had the least incidence of grade 3 or more paclitaxel-HSR in the first cycle of chemotherapy treatment	1 to 3 HOURS
Least incidence of grade 3 or more paclitaxel-HSR second cycle	The treatment group that had the least incidence of grade 3 or more paclitaxel-HSR in the second cycle of chemotherapy treatment	1 to 3 HOURS

Collaborators and Investigators

• Sponsor: Loma Linda University
• Investigators: Principal Investigator: Linda Hong, MD, Loma Linda University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2018
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 16, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 5180198

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No