Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Nausea and Vomiting; Unspecified Adult Solid Tumor, Protocol Specific; Hematopoietic/Lymphoid Cancer

Treatments: Other: Placebo; Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant); Drug: Olanzapine; Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02116530

A221301

U10CA031946 (U.S. NIH Grant/Contract)

NCI-2014-00446 (Other Identifier)

Details and patient eligibility

About

This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. Olanzapine may help prevent chemotherapy-induced nausea and vomiting by blocking brain receptors that appear to be involved in nausea and vomiting.

Full description

Patients with cancer may receive chemotherapy that may cause nausea and vomiting. The purpose of this study is to determine if the use of olanzapine in combination with antiemetic therapy can significantly reduce nausea and vomiting in a large number of patients receiving chemotherapy. Patients are randomized to one of two treatment arms. Please see the "Arms and Intervention" sections for more detailed information. The primary objective is to compare the number of patients with no nausea for the acute (0-24 hours post-chemotherapy), delayed (24-120 hours post-chemotherapy) and overall periods (0-120 hours post-chemotherapy) for patients receiving HEC. The secondary objectives are:

1. To compare the complete response (CR) (no emetic episodes and no use of rescue medication) in the acute, delayed and overall periods
2. To compare the incidences of potential toxicities ascribed to olanzapine

Protocol treatment is to begin ≤ 14 days of registration. Patients will receive treatment on Days 1-4. Patients will be permitted to take rescue therapy of the treating investigator's choice for nausea and/or emesis/retching, based on clinical circumstances. After completing treatment, patients will be monitored for side effects.

Enrollment: 401 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• Diagnosis of malignant disease

• No prior chemotherapy and scheduled to receive HEC (either cisplatin-containing regimen or anthracycline + cyclophosphamide [AC])

  • Cisplatin at a dose of ≥70mg/m^2, with or without other chemotherapy agent(s) OR
  • Anthracycline (60 mg/m^2) plus cyclophosphamide(600 mg/m^2)

• Age ≥18 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2

• Required Initial Laboratory Values ≤ 120 days prior to registration

  • Serum Creatinine ≤2.0 mg/dL
  • Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic oxaloacetic transaminase (SGPT) ≤3 x Upper Limit of Normal (ULN)
  • Absolute neutrophil count (ANC) ≥1500/mm^3

• No nausea or vomiting ≤ 24 hours prior to registration

• Negative pregnancy test (serum or urine) done ≤7 days prior to registration, for women of childbearing potential only (per clinician discretion)

• No severe cognitive compromise

• No known history of CNS disease (e.g. brain metastases, seizure disorder)

• No treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone ≤30 days prior to registration or planned during protocol therapy

• No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy)

• No concurrent use of amifostine

• No concurrent abdominal radiotherapy

• No concurrent use of quinolone antibiotic therapy

• No chronic alcoholism (as determined by the investigator)

• No known hypersensitivity to olanzapine

• No known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the previous six months.

• No history of uncontrolled diabetes mellitus (e.g. on insulin or an oral hypoglycemic agent)

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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401 participants in 2 patient groups

Olanzapine + Chemotherapy + Antiemetic treatment

Experimental group

Description:

Patients will receive the chemotherapy drugs cisplatin or cyclophosphamide and doxorubicin as well as the following anti-nausea/vomiting drugs: * Ondansetron (8 mg orally or intravenously) or granisetron (1 mg intravenously or 2 mg orally) or palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus * Dexamethasone (12 mg orally on the day of chemotherapy and 8 mg orally days 2, 3, 4 post chemotherapy), plus * Fosaprepitant (150 mg intravenously on the day of chemotherapy) or aprepitant (125 mg orally on the day of chemotherapy and 80 mg orally on days 2 and 3 post chemotherapy), plus * olanzapine (10 mg orally on the day of chemotherapy and 10 mg orally on days 2, 3, 4 post chemotherapy)

Treatment:

Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)

Drug: Olanzapine

Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant)

Placebo + Chemotherapy + Antiemetic treatment

Active Comparator group

Description:

Patients will receive the chemotherapy drugs cisplatin or cyclophosphamide and doxorubicin as well as usual anti-nausea/vomiting drugs: * Ondansetron (8 mg orally or intravenously) or granisetron (1 mg intravenously or 2 mg orally) or palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus * Dexamethasone (12 mg orally on the day of chemotherapy and 8 mg orally days 2, 3, 4 post chemotherapy), plus * Fosaprepitant (150 mg intravenously on the day of chemotherapy) or aprepitant (125 mg orally on the day of chemotherapy and 80 mg orally on days 2 and 3 post chemotherapy), plus * placebo

Treatment:

Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)

Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant)

Other: Placebo