Breast CancerPhase 4NCT05841849
Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer
A Phase 4 study testing Aprepitant, Palonosetron and Fosaprepitant in people with Breast Cancer and Chemotherapy-induced Nausea and Vomiting, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
Chemotherapy is one of the most common treatments for breast cancer, but the adverse effects can be severe enough to delay or make chemotherapy intolerable, thus affecting the efficacy of the disease. Women and younger patients are more likely to experience chemotherapy-induced nausea and vomiting (CINV) . Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer, Chemotherapy-induced Nausea and Vomiting
- What is being tested?
- Aprepitant, Palonosetron and Fosaprepitant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,028 participants
- Where
- 1 siteChina
- Study dates
- Jul 2023to Jul 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female, age 18-70 years.
- Confirmed pathology suggested primary invasive breast adenocarcinoma; Presence of adjuvant chemotherapy or neoadjuvant chemotherapy indications according to clinical guidelines.
- No other malignant tumor or other chemotherapy
- No prior treatment for present breast cancer onset
- ECOG physical status score 0 to 1
- Hematological examination before treatment should meet: white blood cell count (WBC) ≥ 4.0×10^9/L, neutrophil count (ANC) ≥ 1.5×10^9/L, platelet count (PLT) ≥ 100×10^9/L; hemoglobin (Hb) ≥ 90g/L; AST (sGOT), ALT (sGPT) ≤ 1.5 times the normal value upper limit, creatinine ≤ 1.5 times the upper limit of normal value, total bilirubin ≤ 1.5 times the upper limit of normal value.
- No serious impairment of heart, liver, kidney and other important organ functions.
Who cannot join
- Unwilling or unable to use an acceptable method of contraception for up to and including 8 weeks after the final dose of the test drug.
- Women during pregnancy and breastfeeding after pregnancy.
- Women with proven distant metastases of breast cancer.
- Patients with proven sensory or motor nerve disease.
- Definite cardiovascular disease, severe co-morbidity or active infection, including known HIV infection.
- Patients who need long-term anticoagulant drugs for cardiovascular or thrombotic diseases.
- History of other tumors.
- Allergic to the study drug or its excipients, etc.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
the Second Affiliated Hospital of Zhejiang Univercity School of Medicine
Hanzhou, Zhejiang
About this study
Official title: Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of Breast Cancer Chemotherapy-induced Nausea and Vomiting: a Single-center, Randomized Controlled Clinical Trial
Chemotherapy is one of the most common treatments for breast cancer, but the adverse effects can be severe enough to delay or make chemotherapy intolerable, thus affecting the efficacy of the disease. Women and younger patients are more likely to experience chemotherapy-induced nausea and vomiting (CINV) . Therefore, antiemetic drugs is a key way to reduce chemotherapy side effects, which ensures compliance, and maintain quality of life. CINV is usually induced by two pathways. The central pathway is mediated by neurokinin-1 (NK-1) receptors, where chemotherapeutic agents stimulate the secretion of substance-P (SP) from the vomiting center located in the medulla oblongata and nucleus accumbens, which binds to NK-1 receptors and induces vomiting. The peripheral pathway is mediated by 5-hydroxytryptamine 3 (5-HT3) receptors, and chemotherapy stimulates intestinal chromophores in the gastrointestinal mucosa to secrete 5-HT3, which binds to its receptors to induce vomiting.
Most guidelines currently recommend the combination of 5-HT3 receptor antagonists, NK-1 receptor antagonists, and dexamethasone for high-emetogenic-risk chemotherapy regimens. Usually 5-HT3 receptor antagonists include granisetron, ondansetron, and palonosetron. Palonosetron is a second-generation 5-HT3 receptor antagonist with stronger affinity and higher efficacy than other antagonists. The commonly used NK-1 receptor antagonists are aprepitant and fosaprepitant. Fosaprepitant is an aprepitant prodrug that can be rapidly converted to aprepitant in the body, blocking the binding of substance P to NK-1 receptors for antiemetic purposes. Clinical trial has confirmed that the overall complete response (CR) rate of palonosetron 0.75 mg combined with fosaprepitant and dexamethasone was 54.9%, with 75.9% CR in the acute phase (0-24 h after chemotherapy) and 62.3% in the delayed phase (24-72 h after chemotherapy). Another clinical trial showed an acute phase CR of 89.8% and a delayed phase CR of 90.4% for oral aprepitant combined with intravenous palonosetron 0.75 mg and dexamethasone. The data suggests that both oral and intravenous administration are effective in preventing CINV, but there are no clinical trial results for oral versus intravenous administration. Oral administration is painless, has fewer side effects, and is a safer mode of administration, but bioavailability is different and drug absorption is affected by a variety of factors; whereas intravenous injection has rapid onset of action, but there are risks of injection reactions, phlebitis, and infection. Therefore, we hope to conduct a non-inferiority study on the efficacy of oral and intravenous 5-HT3 receptor antagonists combined with NK-1 receptor antagonists through this trial, which can provide more options for patients by combining the cost and administration methods.
- Being tested
- Aprepitant, Palonosetron, Fosaprepitant
- Keywords
- breast cancer, CINV, chemotherapy, oral versus intravenous
- Medical subject headings
- Breast Neoplasms, Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AprepitantDrug
oral aprepitant capsules 125mg for D1 before chemotherapy, 80mg for D2 and D3
PalonosetronDrug
oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;
FosaprepitantDrug
intravenous fosaprepitant 150mg for D1 before chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| oral group | Experimental | patients receive oral palonosetron and aprepitant Receives: Drug: Aprepitant; Drug: Palonosetron |
| intravenous group | Active comparator | patients receive intravenous palonosetron and fosaprepitant Receives: Drug: Palonosetron; Drug: Fosaprepitant |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete response
No vomiting or additional antiemetic medication throughout the post-chemotherapy period (0-72 hours)
Measured: 0-72 hour after chemotherapy
Secondary outcomes (2)
delayed phase complete response
Delayed phase (24-72 hours after chemotherapy) without vomiting or additional antiemetic medication use
Measured: 24-72 hour after chemotherapy
acute phase complete response
Acute phase (0-24 hours after chemotherapy) without vomiting or additional antiemetic medication use
Measured: 0-24 hour after chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study startJul 2023 (estimated)
- Primary completionJul 2028 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,028 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05841849
- Sponsor's protocol ID
- 2023-0277
- Status last verified
- Apr 2023
- First submitted
- 23 Apr 2023
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Navari RM, Aapro M. Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Apr 7;374(14):1356-67. doi: 10.1056/NEJMra1515442. No abstract available.
PubMed 27050207Gupta K, Walton R, Kataria SP. Chemotherapy-Induced Nausea and Vomiting: Pathogenesis, Recommendations, and New Trends. Cancer Treat Res Commun. 2021;26:100278. doi: 10.1016/j.ctarc.2020.100278. Epub 2020 Dec 11.
PubMed 33360668Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Lyman GH. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797. doi: 10.1200/JCO.20.01296. Epub 2020 Jul 13.
PubMed 32658626Navari RM. Palonosetron for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2014 Dec;15(17):2599-608. doi: 10.1517/14656566.2014.972366. Epub 2014 Oct 17.
PubMed 25323946Garnock-Jones KP. Fosaprepitant Dimeglumine: A Review in the Prevention of Nausea and Vomiting Associated with Chemotherapy. Drugs. 2016 Sep;76(14):1365-72. doi: 10.1007/s40265-016-0627-7.
PubMed 27510503Matsumoto K, Takahashi M, Sato K, Osaki A, Takano T, Naito Y, Matsuura K, Aogi K, Fujiwara K, Tamura K, Baba M, Tokunaga S, Hirano G, Imoto S, Miyazaki C, Yanagihara K, Imamura CK, Chiba Y, Saeki T. A double-blind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapy-induced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide. Cancer Med. 2020 May;9(10):3319-3327. doi: 10.1002/cam4.2979. Epub 2020 Mar 13.
PubMed 32168551Nakayama Y, Ito Y, Tanabe M, Takahashi S, Hatake K. A combination of aprepitant, palonosetron, and dexamethasone prevents emesis associated with anthracycline-containing regimens for patients with breast cancer. A retrospective study. Breast Cancer. 2015 Mar;22(2):177-84. doi: 10.1007/s12282-013-0472-4. Epub 2013 May 8.
PubMed 23653153
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of Breast Cancer Chemotherapy-induced Nausea and Vomiting: a Single-center, Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT05841849
- Acronym / sponsor ID
- 2023-0277
- Keywords
- breast cancer, CINV, chemotherapy, oral versus intravenous
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,028 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- Jul 2023 (estimated)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 3 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chemotherapy is one of the most common treatments for breast cancer, but the adverse effects can be severe enough to delay or make chemotherapy intolerable, thus affecting the efficacy of the disease. Women and younger patients are more likely to experience chemotherapy-induced nausea and vomiting (CINV) . Therefore, antiemetic drugs is a key way to reduce chemotherapy side effects, which ensures compliance, and maintain quality of life. CINV is usually induced by two pathways. The central pathway is mediated by neurokinin-1 (NK-1) receptors, where chemotherapeutic agents stimulate the secretion of substance-P (SP) from the vomiting center located in the medulla oblongata and nucleus accumbens, which binds to NK-1 receptors and induces vomiting. The peripheral pathway is mediated by 5-hydroxytryptamine 3 (5-HT3) receptors, and chemotherapy stimulates intestinal chromophores in the gastrointestinal mucosa to secrete 5-HT3, which binds to its receptors to induce vomiting.
Most guidelines currently recommend the combination of 5-HT3 receptor antagonists, NK-1 receptor antagonists, and dexamethasone for high-emetogenic-risk chemotherapy regimens. Usually 5-HT3 receptor antagonists include granisetron, ondansetron, and palonosetron. Palonosetron is a second-generation 5-HT3 receptor antagonist with stronger affinity and higher efficacy than other antagonists. The commonly used NK-1 receptor antagonists are aprepitant and fosaprepitant. Fosaprepitant is an aprepitant prodrug that can be rapidly converted to aprepitant in the body, blocking the binding of substance P to NK-1 receptors for antiemetic purposes. Clinical trial has confirmed that the overall complete response (CR) rate of palonosetron 0.75 mg combined with fosaprepitant and dexamethasone was 54.9%, with 75.9% CR in the acute phase (0-24 h after chemotherapy) and 62.3% in the delayed phase (24-72 h after chemotherapy). Another clinical trial showed an acute phase CR of 89.8% and a delayed phase CR of 90.4% for oral aprepitant combined with intravenous palonosetron 0.75 mg and dexamethasone. The data suggests that both oral and intravenous administration are effective in preventing CINV, but there are no clinical trial results for oral versus intravenous administration. Oral administration is painless, has fewer side effects, and is a safer mode of administration, but bioavailability is different and drug absorption is affected by a variety of factors; whereas intravenous injection has rapid onset of action, but there are risks of injection reactions, phlebitis, and infection. Therefore, we hope to conduct a non-inferiority study on the efficacy of oral and intravenous 5-HT3 receptor antagonists combined with NK-1 receptor antagonists through this trial, which can provide more options for patients by combining the cost and administration methods.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| oral group | Experimental | Drug: Aprepitant, Drug: Palonosetronpatients receive oral palonosetron and aprepitant |
| intravenous group | Active comparator | Drug: Palonosetron, Drug: Fosaprepitantpatients receive intravenous palonosetron and fosaprepitant |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Female, age 18-70 years.
- Confirmed pathology suggested primary invasive breast adenocarcinoma; Presence of adjuvant chemotherapy or neoadjuvant chemotherapy indications according to clinical guidelines.
- No other malignant tumor or other chemotherapy
- No prior treatment for present breast cancer onset
- ECOG physical status score 0 to 1
Key exclusion criteria (8 listed)
- Unwilling or unable to use an acceptable method of contraception for up to and including 8 weeks after the final dose of the test drug.
- Women during pregnancy and breastfeeding after pregnancy.
- Women with proven distant metastases of breast cancer.
- Patients with proven sensory or motor nerve disease.
- Definite cardiovascular disease, severe co-morbidity or active infection, including known HIV infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aprepitantoral aprepitant capsules 125mg for D1 before chemotherapy, 80mg for D2 and D3 | Drug | oral group |
| Palonosetronoral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy; | Drug | intravenous group, oral group |
| Fosaprepitantintravenous fosaprepitant 150mg for D1 before chemotherapy | Drug | intravenous group |
Primary outcome
complete response
Time frame: 0-72 hour after chemotherapy
No vomiting or additional antiemetic medication throughout the post-chemotherapy period (0-72 hours)
2 secondary outcomes
delayed phase complete response
Time frame: 24-72 hour after chemotherapy
acute phase complete response
Time frame: 0-24 hour after chemotherapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Background: PubMed 27050207Navari RM, Aapro M. Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Apr 7;374(14):1356-67. doi: 10.1056/NEJMra1515442. No abstract available.
- Background: PubMed 33360668Gupta K, Walton R, Kataria SP. Chemotherapy-Induced Nausea and Vomiting: Pathogenesis, Recommendations, and New Trends. Cancer Treat Res Commun. 2021;26:100278. doi: 10.1016/j.ctarc.2020.100278. Epub 2020 Dec 11.
- Background: PubMed 32658626Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Lyman GH. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797. doi: 10.1200/JCO.20.01296. Epub 2020 Jul 13.
- Background: PubMed 25323946Navari RM. Palonosetron for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2014 Dec;15(17):2599-608. doi: 10.1517/14656566.2014.972366. Epub 2014 Oct 17.
- Background: PubMed 27510503Garnock-Jones KP. Fosaprepitant Dimeglumine: A Review in the Prevention of Nausea and Vomiting Associated with Chemotherapy. Drugs. 2016 Sep;76(14):1365-72. doi: 10.1007/s40265-016-0627-7.
- Background: PubMed 32168551Matsumoto K, Takahashi M, Sato K, Osaki A, Takano T, Naito Y, Matsuura K, Aogi K, Fujiwara K, Tamura K, Baba M, Tokunaga S, Hirano G, Imoto S, Miyazaki C, Yanagihara K, Imamura CK, Chiba Y, Saeki T. A double-blind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapy-induced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide. Cancer Med. 2020 May;9(10):3319-3327. doi: 10.1002/cam4.2979. Epub 2020 Mar 13.
- Background: PubMed 23653153Nakayama Y, Ito Y, Tanabe M, Takahashi S, Hatake K. A combination of aprepitant, palonosetron, and dexamethasone prevents emesis associated with anthracycline-containing regimens for patients with breast cancer. A retrospective study. Breast Cancer. 2015 Mar;22(2):177-84. doi: 10.1007/s12282-013-0472-4. Epub 2013 May 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aprepitant, Palonosetron and Fosaprepitant in people with Breast Cancer and Chemotherapy-induced Nausea and Vomiting, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Tian, doctor (+86 13777825246, denyiweit@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete response (time frame: 0-72 hour after chemotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05841849, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.