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
Conditions
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.
Interventions
Given IV and/or PO
Given IV and/or PO
Given IV and/or PO
Given IV and/or PO
Weekly or every 14 day dosing
Ancillary studies
Given IV and/or PO
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 2 years and 8 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Up to 2 years and 8 months | Will determine whether an abbreviated pre-medication regimen results in an improvement in patient-reported quality of life, as measured by an 11-point numerical analog scale (scores range from 0-10 with higher values representing a worse QoL). Both undesirable appetite increase and reported rash will be rated on this 11-point scale from 0 to 10 with higher values representing a worse undesirable appetite or a worse rash. The worst reported undesirable appetite increase and worst reported rash scores representing the highest mean score reported at an individual time point for each arm, will be summarized. In addition the change from baseline will be summarized by mean separately by treatment arm. Data will be captured every day, for one week after each dose of chemotherapy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Weight Changes Across Study Periods for Both Arms of the Study | 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. |
| Differences in a Number of Symptoms That Might be Improved, or Worsened, by the Hypersensitivity Prevention Drugs | 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. |
| Patient Outcomes | 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. |
| The Impact of Patient Self-reported Allergies | 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. |
| 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) | 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. |
Countries
United States
Participant flow
Pre-assignment details
130 subjects enrolled. 32 not randomized (29 experienced HSR in 1st or 2nd dose of Taxol, 1 ineligible, 2 withdrew). 98 randomized: 50 randomized to continue premeds (4 withdrew after randomization) total of 46 evaluable. 48 randomized to stop premeds (5 withdrew after randomization) total of 43 evaluable.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Paclitaxel, Pre-medications) Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
Cimetidine: Given IV and/or PO
Dexamethasone: Given IV and/or PO
Diphenhydramine: Given IV and/or PO
Famotidine: Given IV and/or PO
Paclitaxel: Weekly or every 14 day dosing
Quality-of-Life Assessment: Ancillary studies
Ranitidine: Given IV and/or PO | 46 |
| Arm II (Paclitaxel) Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
Paclitaxel: Weekly or every 14 day dosing
Quality-of-Life Assessment: Ancillary studies | 43 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | five subjects withdrew due to what they considered to be an unfavorable randomization assignment | 2 | 3 |
| Overall Study | one subject discontinued paclitaxel due to toxicity | 0 | 1 |
| Overall Study | one withdrew without providing a reason | 0 | 1 |
| Overall Study | two subjects withdrew due to perceived side effects of premedications | 2 | 0 |
Baseline characteristics
| Characteristic | Arm I (Paclitaxel, Pre-medications) | Arm II (Paclitaxel) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 9 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 34 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 42 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 7 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 45 Participants | 33 Participants | 78 Participants |
| Region of Enrollment United States | 46 participants | 43 participants | 89 participants |
| Sex: Female, Male Female | 45 Participants | 43 Participants | 88 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
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.
Time frame: Up to 2 years and 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Paclitaxel, Pre-medications) | 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 | 0 Participants |
| Arm II (Paclitaxel) | 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 | 1 Participants |
Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL)
Will determine whether an abbreviated pre-medication regimen results in an improvement in patient-reported quality of life, as measured by an 11-point numerical analog scale (scores range from 0-10 with higher values representing a worse QoL). Both undesirable appetite increase and reported rash will be rated on this 11-point scale from 0 to 10 with higher values representing a worse undesirable appetite or a worse rash. The worst reported undesirable appetite increase and worst reported rash scores representing the highest mean score reported at an individual time point for each arm, will be summarized. In addition the change from baseline will be summarized by mean separately by treatment arm. Data will be captured every day, for one week after each dose of chemotherapy.
Time frame: Up to 2 years and 8 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm I (Paclitaxel, Pre-medications) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Worst reported undesirable appetite increase | 2.5 score on a scale |
| Arm I (Paclitaxel, Pre-medications) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Worst reported rash | 3.3 score on a scale |
| Arm I (Paclitaxel, Pre-medications) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Change in undesirable appetite increase from baseline | 1.7 score on a scale |
| Arm I (Paclitaxel, Pre-medications) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Change in reported rash from baseline | 2.9 score on a scale |
| Arm II (Paclitaxel) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Change in reported rash from baseline | 1.9 score on a scale |
| Arm II (Paclitaxel) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Worst reported undesirable appetite increase | 1 score on a scale |
| Arm II (Paclitaxel) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Change in undesirable appetite increase from baseline | 0.5 score on a scale |
| Arm II (Paclitaxel) | Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL) | Worst reported rash | 2.3 score on a scale |
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 6 years