Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer

NCT ID: NCT03571126

Last Updated: 2021-07-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-09
• Study Completion Date: 2023-08-01

Brief Summary

Chemotherapy induced nausea and vomiting (CINV) is a common adverse effect in treatment of cancer, which influences the quality of life and adherence to treatment of patients and leads to dehydration, malnutrition and even death. Prevention and relieving the CINV is an important step to ensure the conduction of chemotherapy. Mechanism of CINV remains to be obscure, while most studies showed that it is mainly related to the following respects: ⑴ Chemotherapeutic agents stimulate gastrointestinal tract, which induces the release of neurotransmitters by chromaffin cells. Neurotransmitters bind to corresponding receptors, and then results in vomiting by stimulating the vomiting center; ⑵ Chemotherapeutic agents and the metabolites of them activate chemoreceptors directly, which causes vomiting. ⑶ Feeling and mental factors irritate cerebral cortex pathway directly. There are studies suggested that 5- hydroxytryptamine (5-HT) was related to acute nausea and vomiting induced by chemotherapy, which means 5-HT receptor antagonist would be a effective medicine for acute CINV. In addition, there are researches proclaimed that neurokinin-1 (NK-1) receptor antagonist, aprepitant, is a potent agent to relieve CINV. Thus, correlative guidelines recommend regimens with 5-HT receptor antagonist, NK-1 receptor antagonist and glucocorticoid as the standard treatment for strongly emetic chemotherapy regimens. But the prevention of moderately emetic chemotherapy regimens remains to be a problem in clinical practice. Besides, there is no study to demonstrate differences of mechanisms between acute CINV and delayed CINV. Olanzapine inhibits kinds of neurotransmitters which cause CINV, it is why this medicine is effective in both acute and delayed CINV. It can also alleviate anxiety, improve sleep quality and relieve pain in patients with cancer. The most common adverse effects of olanzapine are lethargy, body mass increase, fatigue, dry mouth, constipation, hyperlipidemia and hyperglycemia. Among them, the most common one is lethargy, which can oppose insomnia and excitation caused by dexamethasone. In a word, olanzapine is an agent with mild adverse effects, it is worth to be generalized. But there are still problems to be resolved in the application of olanzapine in CINV: ⑴ Aprepitant is expensive and not covered in medical care in China, which limits the application in patients. ⑵There is no large clinical trial to confirm the efficacy and safety of olanzapine in Chinese populations. To explore these issues better, investigators intend to compare the regimen with olanzapine, dexamethasone and 5-HT receptor antagonists with the regimen with placebo, dexamethasone and 5-HT receptor antagonists about the efficacy and adverse events in treatment of CINV. Investigators aim to provide an available therapeutic options for CINV, improve the quality of life and prolong the survival of patients with lung cancer.

Conditions

Chemotherapy-induced Nausea and Vomiting; Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebos group

Patients will be administered with dexamethasone plus tropisetron from D1 to D3.

Patients will also be administrated with placebos from D1-D4

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Dexamethasone (10mg/d) (Days1-3) Tropisetron (4mg or 4.48mg or 5mg /d) (Days1-3) Placebos (Days1-4)

Experimental group

Patients will receive a regimen with dexamethasone plus tropisetron from D1-D3. Patients will also be administrated with olanzapine from D1-D4.

Group Type: EXPERIMENTAL

Olanzapine

Intervention Type: DRUG

Dexamethasone (10mg/d) (Days1-3) Tropisetron (4mg or 4.48mg or 5mg /d) (Days1-3) Olanzapine (10mg/d) (Days1-4)

Interventions

Olanzapine

Dexamethasone (10mg/d) (Days1-3) Tropisetron (4mg or 4.48mg or 5mg /d) (Days1-3) Olanzapine (10mg/d) (Days1-4)

Intervention Type: DRUG

Placebos

Dexamethasone (10mg/d) (Days1-3) Tropisetron (4mg or 4.48mg or 5mg /d) (Days1-3) Placebos (Days1-4)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) Performance Status≤2 or Karnofsky performance statu (KPS) scores≥60.

2. Patients with cytologically or histologically confirmed lung cancer.

3. Patients who are willing to receive chemotherapy and can tolerate at least 2 cycles chemotherapy.

4. Chemotherapy regimens accord with standard regimens recommended by clinical practice guidelines (National Comprehensive Cancer Network guidelines and Chinese Society of Clinical Oncology guidelines of lung cancer).

5. There is at least one kind of high emetic risk chemotherapy agent, mainly including regimens contain cisplatin or carboplatin (AUC≥4).

6. Adequate organ function including the following: Adequate bone marrow reserve: white blood cell (WBC) count superior or equal to 2.0×10^9/L , absolute neutrophil count (ANC) superior or equal to 1.5×10^9/L, platelets superior or equal to 80×10^9/L, and hemoglobin superior or equal to 90g/L; Hepatic: bilirubin <1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5×ULN (or <5×ULN with liver metastases); Renal: Serum creatinine≤1×ULN, calculated creatinine clearance (CrCl) superior or equal to 50 milliliter/min based on the standard Cockcroft and Gault formula.

7. At least 3 weeks after the end of the last chemotherapy.

8. Women of reproductive years are willing to contracept in appropriate methods in the period of trial and in the 8 weeks after the last administration. Doing pregnancy test before the beginning of this trial when necessary, and results of which need to be negative.

Exclusion Criteria

1. Women who are pregnant or breastfeeding

2. Need to undergo radiotherapy during this trial.

3. Patients with alimentary tract obstruction.

4. Patients with severe heart disease, renal and liver disease and metabolic abnormalities.

5. Patients with epilepsy or who are using antipsychotics.

6. Patients who have been administrated with antiemetic in 24 hours or who have suffered vomiting before chemotherapy.

7. Patients with brain metastases.

8. Patients with contraindications of chemotherapy.

9. Patients who are attending another clinical trial or will attend in 2 weeks.

10. Patients who are considered unsuitable to be included by treating physicians.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zunyi First People's Hospital

INDUSTRY

Sponsor Role: collaborator

Affiliated Hospital of North Sichuan Medical College

OTHER

Sponsor Role: collaborator

Sichuan Cancer Hospital and Research Institute

OTHER

Sponsor Role: collaborator

Guizhou Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Affiliated Hospital of Southwest Medical University

OTHER

Sponsor Role: collaborator

Zunyi Medical College

OTHER

Sponsor Role: lead

Responsible Party

Jian-Guo Zhou,MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hu Ma, Doctor

Role: PRINCIPAL_INVESTIGATOR

Zunyi Medical College

Locations

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, China

Site Status: RECRUITING

Affiliated Hospital of North Sichuan Medical College

Nanchong, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

JianGuo Zhou, Master

Role: CONTACT

jianguo.zhou@yahoo.com

+86 18311543939

PeiJie Li, Bachelor

Role: CONTACT

503186082@qq.com

+86 18166955040

Facility Contacts

Jian-Guo Zhou

Role: primary

jianguo.zhou@yahoo.com

18311543939

Xian-Bang Tan, MD

Role: primary

References

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Reference Type: BACKGROUND

PMID: 28759346 (View on PubMed)

Adel N. Overview of chemotherapy-induced nausea and vomiting and evidence-based therapies. Am J Manag Care. 2017 Sep;23(14 Suppl):S259-S265.

Reference Type: BACKGROUND

PMID: 28978206 (View on PubMed)

Navari RM. 5-HT3 receptors as important mediators of nausea and vomiting due to chemotherapy. Biochim Biophys Acta. 2015 Oct;1848(10 Pt B):2738-46. doi: 10.1016/j.bbamem.2015.03.020. Epub 2015 Mar 30.

Reference Type: BACKGROUND

PMID: 25838122 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 22024310 (View on PubMed)

Geling O, Eichler HG. Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol. 2005 Feb 20;23(6):1289-94. doi: 10.1200/JCO.2005.04.022.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Passik SD, Kirsh KL, Theobald DE, Dickerson P, Trowbridge R, Gray D, Beaver M, Comparet J, Brown J. A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. J Pain Symptom Manage. 2003 May;25(5):485-8. doi: 10.1016/s0885-3924(03)00078-2.

Reference Type: BACKGROUND

PMID: 12727048 (View on PubMed)

Zhang Z, Zhang Y, Chen G, Hong S, Yang Y, Fang W, Luo F, Chen X, Ma Y, Zhao Y, Zhan J, Xue C, Hou X, Zhou T, Ma S, Gao F, Huang Y, Chen L, Zhou N, Zhao H, Zhang L. Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis. Oncologist. 2018 May;23(5):603-616. doi: 10.1634/theoncologist.2017-0378. Epub 2018 Jan 12.

Reference Type: BACKGROUND

PMID: 29330211 (View on PubMed)

Other Identifiers

20180520

Identifier Type: -

Identifier Source: org_study_id