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

Phase 2
Completed
Conditions
Anatomic Stage I Breast Cancer AJCC v8
Prognostic Stage IIIA Breast Cancer AJCC v8
Prognostic Stage IV Breast Cancer AJCC v8
Anatomic Stage 0 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
Interventions
Registration Number
NCT04862585
Lead Sponsor
Ohio State University Comprehensive Cancer Center
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
129
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I (paclitaxel, pre-medications)Quality-of-Life AssessmentPatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm II (paclitaxel)Quality-of-Life AssessmentPatients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
Arm I (paclitaxel, pre-medications)CimetidinePatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm I (paclitaxel, pre-medications)RanitidinePatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm I (paclitaxel, pre-medications)DexamethasonePatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm I (paclitaxel, pre-medications)DiphenhydraminePatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm I (paclitaxel, pre-medications)FamotidinePatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm I (paclitaxel, pre-medications)PaclitaxelPatients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Arm II (paclitaxel)PaclitaxelPatients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
Primary Outcome Measures
NameTimeMethod
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 dosingUp to 6 years

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
NameTimeMethod
Correlation between abbreviated premedication regimen results to quality of life (QoL)Up to 6 years

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.

Trial Locations

Locations (1)

Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

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