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

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ClinicalTrials.gov Identifier: NCT04862585
Recruitment Status : Recruiting
First Posted : April 28, 2021
Last Update Posted : October 22, 2021
Sponsor:
Information provided by (Responsible Party):
Michael Berger, 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.

Condition or disease Intervention/treatment Phase
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 Drug: Cimetidine Drug: Dexamethasone Drug: Diphenhydramine Drug: Famotidine Drug: Paclitaxel Other: Quality-of-Life Assessment Drug: Ranitidine Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Safely Stopping Pre-Medications in Patients Receiving Paclitaxel: A Randomized Trial
Actual Study Start Date : October 7, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

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.
Drug: Cimetidine
Given IV and/or PO
Other Name: Tagamet

Drug: Dexamethasone
Given IV and/or PO
Other Names:
  • 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

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:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

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.
Drug: Paclitaxel
Weekly or every 14 day dosing
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. 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 [ Time Frame: Up 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 :
  1. Correlation between abbreviated premedication regimen results to quality of life (QoL) [ Time Frame: 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.


Other Outcome Measures:
  1. Differences in a number of symptoms that might be improved, or worsened, by the hypersensitivity prevention drugs [ Time Frame: Up to 6 years ]
    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.

  2. 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) [ Time Frame: Up to 6 years ]
    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.

  3. Weight changes across study periods for both arms of the study [ Time Frame: Up to 6 years ]
    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.

  4. The impact of patient self-reported allergies [ Time Frame: Up to 6 years ]
    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.

  5. Patient outcomes [ Time Frame: Up to 6 years ]
    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.

  6. Reaction rate [ Time Frame: Up to 6 years ]
    Reaction rate will be summarized by paclitaxel manufacturer and lot number.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients scheduled to receive at least 4 doses of paclitaxel as a single-agent or in combination with trastuzumab, pertuzumab, bevacizumab, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04862585


Contacts
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Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations
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United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Michael J. Berger, Pharm.D.    614-366-0556    Michael.Berger@osumc.edu   
Principal Investigator: Michael J. Berger, Pharm.D.         
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
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Principal Investigator: Michael J Berger, Pharm.D. Ohio State University Comprehensive Cancer Center
Additional Information:
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Responsible Party: Michael Berger, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT04862585    
Other Study ID Numbers: OSU-20429
NCI-2021-01586 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: April 28, 2021    Key Record Dates
Last Update Posted: October 22, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Breast Carcinoma In Situ
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Diphenhydramine
Promethazine
Dexamethasone
Dexamethasone acetate
Paclitaxel
Albumin-Bound Paclitaxel
Famotidine
Ranitidine
Cimetidine
BB 1101
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents