Clinical trial NCT04862585: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: 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
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2021-04-28
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: 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
timeFrame: Up to 6 years
Secondary outcomes:
measure: Correlation between abbreviated premedication regimen results to quality of life (QoL)
timeFrame: Up to 6 years
Other outcomes:
measure: Differences in a number of symptoms that might be improved, or worsened, by the hypersensitivity prevention drugs
timeFrame: Up to 6 years
measure: 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)
timeFrame: Up to 6 years
measure: Weight changes across study periods for both arms of the study
timeFrame: Up to 6 years
measure: The impact of patient self-reported allergies
timeFrame: Up to 6 years
measure: Patient outcomes
timeFrame: Up to 6 years
measure: Reaction rate
timeFrame: Up to 6 years
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Michael J Berger, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: