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

Primary Purpose

Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cimetidine
Dexamethasone
Diphenhydramine
Famotidine
Paclitaxel
Quality-of-Life Assessment
Ranitidine
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Anatomic Stage 0 Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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), a steroid (dexamethasone) and a histamine-2 (H2) antagonist (either famotidine, ranitidine or cimetidine), 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

Sites / Locations

  • Ohio State University Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I (paclitaxel, pre-medications)

Arm II (paclitaxel)

Arm Description

Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
April 23, 2021
Last Updated
February 7, 2023
Sponsor
Ohio State University Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04862585
Brief Title
Safely Stopping Pre-medications in Patients With Breast Cancer Who Are Receiving Paclitaxel
Official Title
Safely Stopping Pre-Medications in Patients Receiving Paclitaxel: A Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 7, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anatomic Stage 0 Breast Cancer AJCC v8, 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, Anatomic Stage IV Breast Cancer AJCC v8, Breast Carcinoma, Prognostic Stage 0 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, Prognostic Stage IV Breast Cancer AJCC v8

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (paclitaxel, pre-medications)
Arm Type
Active Comparator
Arm Description
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm Title
Arm II (paclitaxel)
Arm Type
Experimental
Arm Description
Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
Intervention Type
Drug
Intervention Name(s)
Cimetidine
Other Intervention Name(s)
Tagamet
Intervention Description
Given IV and/or PO
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
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, 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
Intervention Description
Given IV and/or PO
Intervention Type
Drug
Intervention Name(s)
Diphenhydramine
Other Intervention Name(s)
FAR 90X2, PM 255, Probedryl, Rigidyl, S51, Syntedril
Intervention Description
Given IV and/or PO
Intervention Type
Drug
Intervention Name(s)
Famotidine
Other Intervention Name(s)
Pepcid, Pepcid AC
Intervention Description
Given IV and/or PO
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Weekly or every 14 day dosing
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Drug
Intervention Name(s)
Ranitidine
Intervention Description
Given IV and/or PO
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Correlation between abbreviated premedication regimen results to quality of life (QoL)
Description
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.
Time Frame
Up to 6 years
Other Pre-specified Outcome Measures:
Title
Differences in a number of symptoms that might be improved, or worsened, by the hypersensitivity prevention drugs
Description
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.
Time Frame
Up to 6 years
Title
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)
Description
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.
Time Frame
Up to 6 years
Title
Weight changes across study periods for both arms of the study
Description
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.
Time Frame
Up to 6 years
Title
The impact of patient self-reported allergies
Description
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.
Time Frame
Up to 6 years
Title
Patient outcomes
Description
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.
Time Frame
Up to 6 years
Title
Reaction rate
Description
Reaction rate will be summarized by paclitaxel manufacturer and lot number.
Time Frame
Up to 6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
The Ohio State University Comprehensive Cancer Center
Phone
800-293-5066
Email
OSUCCCClinicaltrials@osumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael J Berger, Pharm.D.
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael J. Berger, Pharm.D.
Phone
614-366-0556
Email
Michael.Berger@osumc.edu
First Name & Middle Initial & Last Name & Degree
Michael J. Berger, Pharm.D.

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://cancer.osu.edu
Description
The Jamesline

Learn more about this trial

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

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