Granisetron Transdermal Patch for Prophylaxis of Delayed CINV

Sponsor

Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04912271

Collaborator

(none)

140

Enrollment

Arms

30.7

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Transdermal granisetron has been shown to as effective as oral/ intravenous granisetron when administered with or without dexamethasone. However, it has not been evaluated specifically against the delayed response of chemotherapy-induced nausea and vomiting (CINV) in comparison with palonosetron, as the complete response for the delayed phase was not reported in the comparative study by Seol et al (Support Care Cancer 2016;24:945-952). Thus, transdermal granisetron needs to be compared with palonosetron as part of dual and triple therapy in the delayed phase of CINV.

This investigator-initiated study aims to compare the efficacy of granisetron transdermal patch and palonosetron combined with NK-1 receptor antagonist and dexamethasone in the prevention of delayed CINV in Chinese breast cancer patients who received high emetic or moderate emetic chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Nausea and Vomiting (CINV)	Drug: Granisetron transdermal patch Drug: Palonosetron Drug: Aprepitant Drug: Fosaprepitant Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Granisetron Transdermal Delivery System Versus Palonosetron in the Prevention of Delayed Chemotherapy-induced Nausea and Vomiting: a Phase 3 Non-inferiority Randomized Trial

Anticipated Study Start Date :

Jun 10, 2021

Anticipated Primary Completion Date :

Jun 10, 2022

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Granisetron transdermal patch (other name: sancuso), aprepitant or fosaprepitant, dexamethasone Patients received granisetron transdermal patch plus dexamethasone followed by oral aprepitant or fosaprepitant infusion Granisetron transdermal patch Aprepitant 125 mg PO D1, 80 mg PO D2-D3; Fosaprepitant 150 mg IV D1 Dexamethasone 7.5-10 mg IV/PO D1	Drug: Granisetron transdermal patch Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. Other Names: sancuso Drug: Aprepitant Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors. Drug: Fosaprepitant Fosaprepitant is a neurokinin-1 receptor antagonist, approved for the prevention of chemotherapy-induced nausea and vomiting. Drug: Dexamethasone Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting.
Active Comparator: Palonosetron, aprepitant or fosaprepitant, dexamethasone Patients received intravenous palonosetron plus dexamethasone followed by oral aprepitant or fosaprepitant infusion Palonosetron 0.25 mg IV D1 Aprepitant 125 mg PO D1, 80 mg PO D2-D3; Fosaprepitant 150 mg IV D1 Dexamethasone 7.5-10 mg IV/PO D1	Drug: Palonosetron Palonosetron is a second-generation 5-HT3 receptor antagonist with proposed higher efficacy and sustained action for prophylaxis of postoperative nausea and vomiting (PONV). Drug: Aprepitant Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors. Drug: Fosaprepitant Fosaprepitant is a neurokinin-1 receptor antagonist, approved for the prevention of chemotherapy-induced nausea and vomiting. Drug: Dexamethasone Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting.

Arm

Intervention/Treatment

Experimental: Granisetron transdermal patch (other name: sancuso), aprepitant or fosaprepitant, dexamethasone

Patients received granisetron transdermal patch plus dexamethasone followed by oral aprepitant or fosaprepitant infusion Granisetron transdermal patch Aprepitant 125 mg PO D1, 80 mg PO D2-D3; Fosaprepitant 150 mg IV D1 Dexamethasone 7.5-10 mg IV/PO D1

Drug: Granisetron transdermal patch

Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting.

Other Names:

sancuso

Drug: Aprepitant

Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors.

Drug: Fosaprepitant

Fosaprepitant is a neurokinin-1 receptor antagonist, approved for the prevention of chemotherapy-induced nausea and vomiting.

Drug: Dexamethasone

Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting.

Active Comparator: Palonosetron, aprepitant or fosaprepitant, dexamethasone

Patients received intravenous palonosetron plus dexamethasone followed by oral aprepitant or fosaprepitant infusion Palonosetron 0.25 mg IV D1 Aprepitant 125 mg PO D1, 80 mg PO D2-D3; Fosaprepitant 150 mg IV D1 Dexamethasone 7.5-10 mg IV/PO D1

Drug: Palonosetron

Palonosetron is a second-generation 5-HT3 receptor antagonist with proposed higher efficacy and sustained action for prophylaxis of postoperative nausea and vomiting (PONV).

Drug: Aprepitant

Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors.

Drug: Fosaprepitant

Fosaprepitant is a neurokinin-1 receptor antagonist, approved for the prevention of chemotherapy-induced nausea and vomiting.

Drug: Dexamethasone

Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting.

Outcome Measures

Primary Outcome Measures

complete response (CR) in delay phase of CINV [From 24 hours after initiating administration of chemotherapy agents to day 7 (24-168 hours)]
To compare the complete response (CR) of Granisetron transdermal patch to Palonosetron (complete response is defined as no vomiting and no rescue medication) in delay phase of CINV

Secondary Outcome Measures

complete response (CR) in the acute and overall phase of CINV [From 24 hours after initiating administration of chemotherapy agents to day 7 (24-168 hours)]
1. To compare the complete response (CR) of Granisetron transdermal patch to Palonosetron (complete response is defined as no vomiting and no rescue medication) in the acute and overall phase of CINV
complete control (CC) in delay phase of CINV [From 24 hours after initiating administration of chemotherapy agents to day 7 (24-168 hours)]
2. To compare the complete control (CC) of Granisetron transdermal patch to Palonosetron (complete control is defined as no vomiting, mild nausea and no rescue medication) in delay phase of CINV
complete control (CC) in the acute and overall phase of CINV [From initiating administration of chemotherapy agents to day 1 (0-24 hours) and day 7 (0-168 hours)]
3. To compare the complete control (CC) of Granisetron transdermal patch to Palonosetron (complete control is defined as no vomiting and no rescue medication) in the acute and overall phase of CINV
Patients' satisfaction with antiemetic therapy (assessed using a 10-cm visual analog scale at the time of patch removal [7 days]
"dissatisfied" on the left end (0 cm) of visual analog scale and the "very satisfied" on the right end of visual analog scale (10 cm)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female aged ≥ 18 years;
Pathologically confirmed breast cancer;
The physical status score ECOG ≤ 2;
Life expectancy of ≥3 months;
Patients first or had already received chemotherapy;
Patients scheduled to receive HEC/MEC chemotherapy, and the main emetic drugs will be used within a single day;
Patients first use of granisetron transdermal patch;
In accordance with the indication of chemotherapy and basic requirements;

Peripheral haematology: Hb ≥8.0g/dL; absolute neutrophil count≥1.5×109/L; platelet count ≥80×109/L
Blood biochemistry: Total bilirubin < 1.5×ULN, ALT and AST ≤ 2.5×ULN; if liver metastasis, ALT and AST < 5×ULN, creatinine ≤ 1.5×ULN

Patients voluntarily participate and sign the informed consent form;
Be able to read, understand and complete patient diaries independently.

Exclusion Criteria:

Contraindicated to 5-HT receptor antagonists, NK-1 receptor antagonist or dexamethasone;
Patients have used 5-HT receptor antagonist, NK1 receptor antagonist or any study drugs within 4 weeks before chemotherapy
Any nausea and vomiting (II or above) within 72 hours before the start of chemotherapy;
According to the judgment of the investigators, there are concomitant diseases (including but not limited to hypertension, severe diabetes, active infection, thyroid disease, etc.) that seriously endanger the safety of the patient or affect the completion of the study;
Patients scheduled to receive radiotherapy of whole body, brain or upper abdomen;
Confirmed by craniocerebral CT or MRI, patients with brain tumor lesions or patients taking drugs to treat brain tumors or epileptic symptoms;
History of drug abuse and alcohol dependence;
Pregnancy, lactation or intended pregnancy;
History of allergic reactions to drugs with similar chemical structures, or to transdermal therapeutic systems, including commercial dressings such as Elastoplast®
Unable to swallow, having intestinal obstruction, or other factors that affect the taking and absorption of the drug;
Long-term use of any inhibitors or inducers of CYP3A4, or take these drugs within 4 weeks before the first day of chemotherapy;
Other situations evaluated by investigators as unsuitable for enrollment.