Safely Stopping Pre-medications in Patients With Breast Cancer Who Are Receiving Paclitaxel

Safely Stopping Pre-Medications in Patients Receiving Paclitaxel: A Randomized Trial

This phase II/III trial investigates the difference in rates of infusion hypersensitivity reaction in patients with breast cancer who are receiving paclitaxel alone or in combination with other cancer drugs which require parenteral rescue medication after stopping standard pre-medications (dexamethasone, diphenhydramine, famotidine/cimetidine/ranitidine), compared to continuing premedications. Paclitaxel is a drug used to treat breast cancer, ovarian cancer, and autoimmune deficiency syndrome (AIDS)-related Kaposi sarcoma. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. However, there are side-effects and toxicities associated with repeat exposure to this pre-medication regimen. With prolonged use of paclitaxel, especially during weekly regimens, patients are exposed to repeat doses of drugs that prevent hypersensitivity reactions. Side effects include, but are not limited to, insomnia, gastritis, fluid retention, weight gain, mood changes and immune suppression. The information gained from this study may positively influence clinical practice and help researchers develop methods to safely stop pre-medications.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Breast Carcinoma; Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Anatomic Stage 0 Breast Cancer AJCC v8; Prognostic Stage 0 Breast Cancer AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Drug: Cimetidine; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Famotidine; Drug: Paclitaxel; Drug: Ranitidine

Detailed Description

PRIMARY OBJECTIVE:

I. To estimate the difference in rates of infusion hypersensitivity reaction (HSR) requiring parenteral rescue medications following the discontinuation of pre-medications after 2 doses of paclitaxel, compared to continuing premedications, in breast cancer patients who have not experienced an infusion HSR with their first 2 paclitaxel doses.

OUTLINE:

Patients receive paclitaxel per standard of care as a single agent or in combination with dexamethasone intravenously (IV) and/or orally (PO), diphenhydramine IV and/or PO and either famotidine IV and/or PO, ranitidine IV and/or PO or cimetidine IV and/or PO. Patients who don't experience any infusion hypersensitivity reaction after the first 2 doses of paclitaxel are randomized to 1 of 2 arms.

ARM I (STANDARD OF CARE): Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.

ARM II (EXPERIMENTAL): Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: Michael J. Berger, Pharm.D.; Phone Number: 614-366-0556; Email: Michael.Berger@osumc.edu
      • Principal Investigator: Michael J. Berger, Pharm.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients scheduled to receive at least 4 doses of paclitaxel as a single-agent or in combination with trastuzumab, pertuzumab, bevacizumab, pembrolizumab, lapatinib, gemcitabine or other drug combination (excluding cisplatin or carboplatin) for the treatment of any stage, histologically confirmed breast cancer
• Ability to complete questionnaires by themselves or with assistance
• Life expectancy > 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age >= 18
• Able to give informed consent
• Patients must be scheduled to receive prophylactic HSR premedications (IV or oral) consisting of a histamine-1 (H1) antagonist (diphenhydramine) or cetirizine (a histamine-1 (H1) antagonists), dexamethasone (a steroid) and a either famotidine, ranitidine or cimetidine (histamine-2 (H2) antagonists), per institutional guidelines, prior to each of their first 2 doses of paclitaxel
• Patients may enroll, or currently be enrolled in another concurrent clinical trial provided the other trial would not prohibit the discontinuation of paclitaxel premedications

Exclusion Criteria:

• Patients who have received at least 1 prior lifetime dose of paclitaxel or paclitaxel albumin-bound
• Patients receiving paclitaxel in combination with carboplatin or cisplatin (due to risk of hypersensitivity with platinum compounds)
• History of grade 3 hypersensitivity reaction to Cremophor EL containing medications (e.g. paclitaxel, cyclosporine, ixabepilone, teniposide)
• Patients receiving therapeutic daily doses of systemic corticosteroids. Intermittent oral steroids for nausea or for acute inflammatory conditions (i.e. methylprednisolone dosepak) and inhaled, intranasal or topical corticosteroids are permitted
• Patients who are pregnant or nursing. Paclitaxel is classified by the Food and Drug Administration (FDA) as "pregnancy category D". Pregnancy testing (urine or blood human chorionic gonadotropin [Hcg]) will be done and documented prior to enrollment if pregnancy is clinically suspected

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (paclitaxel, pre-medications); Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Drug: Cimetidine; Given IV and/or PO; Other Names: Tagamet; Drug: Dexamethasone; Given IV and/or PO; Other Names: Decadron; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Diphenhydramine; Given IV and/or PO; Other Names: FAR 90X2; PM 255; Probedryl; Rigidyl; S51; Syntedril; Drug: Famotidine; Given IV and/or PO; Other Names: Pepcid; Pepcid AC; Drug: Paclitaxel; Weekly or every 14 day dosing; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Ranitidine; Given IV and/or PO
Experimental: Arm II (paclitaxel); Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Drug: Paclitaxel; Weekly or every 14 day dosing; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with grade 2 or greater reactions that require parenteral rescue medications to treat an infusion hypersensitivity reaction (HSR) after the first 2 doses of paclitaxel with or without continued premedication dosing	The proportion of patients having infusion HSR of grade 2 or greater requiring parental treatment (rescue medications) will be estimated along with a 95% confidence interval. The difference in proportions of patients with grade 2 or greater infusion HSR needing rescue medication will be estimated along with a 95% confidence interval using the Z-test of normal approximations of the binomial distributions. As a sensitivity analysis, will repeat the analysis including patients assigned to the discontinuation arm but decided to restart pre-medications and patients assigned to the continuation arm but demanded to have premedications discontinued as having experienced HSR.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between abbreviated premedication regimen results to quality of life (QoL)	Will determine whether an abbreviated pre-medication regimen results in improvement in patient-reported quality of life, as measured by an 11-point numerical analog scale. Patient-reported quality of life, based on a single item 11-point numerical analog scale at each time point as well as change from baseline will be summarized by median (range) separately by treatment arm. Median (mean) QoL scores will be plotted longitudinally by treatment arm. QoL change from baseline will be compared between arms using the Wilcoxon rank-sum test. Data will be captured every day, for one week after each dose of chemotherapy.	Up to 6 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in a number of symptoms that might be improved, or worsened, by the hypersensitivity prevention drugs	Each symptom will be summarized by median (range) at each time point by treatment arm and the weekly average will be compared between arms using the Wilcoxon rank sum test.	Up to 6 years
The number of patients who, after discontinuing pre-medications, request that the premedications be resumed to ameliorate side-effects that the patient thinks have worsened since premedications were stopped (i.e. nausea, rash, arthralgia)	The frequency and percentages of patients who, after discontinuing pre-medications, request that the pre-medications be resumed to ameliorate side-effects that the patient thinks have worsened since pre-medications were stopped (i.e. nausea, rash, arthralgia) will be summarized.	Up to 6 years
Weight changes across study periods for both arms of the study	Weight changes over time will be summarized at each time point using mean (standard deviation) and plotted by treatment arm. Weight change from baseline to 10 weeks post-randomization will be compared between arms that receive weekly paclitaxel using a t-test of two independent samples.	Up to 6 years
The impact of patient self-reported allergies	Will report the impact of patient self-reported allergies, prior to starting paclitaxel (2 or more versus 3 or less), on the incidence of infusion HSR and rescue medication usage. Frequency of patient self-reported allergies (2 or more versus less) on the incidence of infusion HSR and rescue medication usage will be tabulated.	Up to 6 years
Patient outcomes	The rates of rescue medication by arms will be estimated by race/ethnicity group to explore whether there is a differential effect from stopping hypersensitivity reaction by race/ethnicity.	Up to 6 years
Reaction rate	Reaction rate will be summarized by paclitaxel manufacturer and lot number.	Up to 6 years

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Michael J Berger, Pharm.D., Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Carcinoma in Situ; Breast Neoplasms; Breast Carcinoma In Situ; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Hypnotics and Sedatives; Cytochrome P-450 Enzyme Inhibitors; Anesthetics, Local; Anti-Ulcer Agents; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Paclitaxel; Diphenhydramine; Promethazine; Albumin-Bound Paclitaxel; Famotidine; Ranitidine; Cimetidine
• Other Study ID Numbers: OSU-20429; NCI-2021-01586 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No