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

• ClinicalTrials.gov Identifier: NCT02116530
• Recruitment Status: Completed
• First Posted: April 17, 2014
• Results First Posted: April 10, 2017
• Last Update Posted: May 7, 2020
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Tracking Information

• First Submitted Date: April 15, 2014
• First Posted Date: April 17, 2014
• Results First Submitted Date: December 7, 2016
• Results First Posted Date: April 10, 2017
• Last Update Posted Date: May 7, 2020
• Study Start Date: August 2014
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2017)

Proportion of Patients With no Nausea [ Time Frame: 0 to 120 hours after chemotherapy ]

No nausea was defined as a response of 0 in the nausea item of Nausea and Vomiting Daily Diary/Questionnaire in the acute (0-24 hours), delayed (25-120 hours) and overall (0-120 hours) periods after chemotherapy.

• Original Primary Outcome Measures (submitted: April 16, 2014): Proportion of patients with no nausea, defined as a response of 0 in the nausea item of Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 5 days ]

Current Secondary Outcome Measures (submitted: February 27, 2017)

• Median Nausea Scores [ Time Frame: Baseline and Day 2 to Day 6 after chemotherapy ]
  Nausea scores was measured using a visual-analogue scale ranging from 0 (none) to 10 (as bad as it can be).
• Proportion of Patients With Complete Response [ Time Frame: 0 to 120 hours after chemotherapy ]
  Complete response was defined as no emetic episodes and no use of rescue medication during the acute (0-24 hours), delayed (25-120 hours) and overall (0-120 hours) periods as measured by the Nausea and Vomiting Daily Diary/Questionnaire.
• Mean Scores of Potential Toxicities Related to Olanzapine as Measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Baseline and day 2 to 6 days after chemotherapy ]
  Patients were asked to record daily levels of undesired sedation and appetite increase using a visual-analogue scale ranging from 0 (none) to 10 (as bad as it can be).
• Frequency of Rescue Medication [ Time Frame: Day 2 to Day 6 after chemotherapy ]
  Patients were asked to record daily number of extra nausea/vomiting pills taken because they developed nausea/vomiting in the following categories: None, One, Two, More than two in Nausea and Vomiting Daily Diary Questionnaire.

Original Secondary Outcome Measures (submitted: April 16, 2014)

• Nausea scores measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 5 days ]
• Complete response, defined as no emetic episodes and no use of rescue medication measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 5 days ]
• Incidence of potential toxicities related to olanzapine as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 5 days ]
• Frequency of rescue medication repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 5 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy
• Official Title: Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Randomized, Double-Blind, Placebo-Controlled Trial
• Brief Summary: 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care

Condition

• Hematopoietic/Lymphoid Cancer
• Nausea and Vomiting
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

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

Study Arms

• Experimental: Olanzapine + Chemotherapy + Antiemetic treatment

  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)
  Interventions:

  • Drug: Olanzapine
  • Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)
  • Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant)
• Active Comparator: Placebo + Chemotherapy + Antiemetic treatment

  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
  Interventions:

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

• Publications *: Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. doi: 10.1056/NEJMoa1515725.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 27, 2017): 401
• Original Estimated Enrollment (submitted: April 16, 2014): 372
• Actual Study Completion Date: November 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02116530
• Other Study ID Numbers: A221301; NCI-2014-00446 ( Other Identifier: NCI Clinical Trial Reporting Program ); U10CA031946 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alliance for Clinical Trials in Oncology
• Original Responsible Party: Same as current
• Current Study Sponsor: Alliance for Clinical Trials in Oncology
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Rudolph M. Navari, MD, PhD, FACP; Indiana University School of Medicine South Bend

• PRS Account: Alliance for Clinical Trials in Oncology
• Verification Date: April 2020