Dolasetron Mesylate and Dexamethasone With or Without Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancy

A Pilot Study to Evaluate the Safety and Efficacy of Aprepitant in Combination With Dolasetron and Dexamethasone for the Prevention of Nausea and Vomiting Following Oxaliplatin-containing Regimen Which Includes 5-FU.

This randomized pilot clinical trial dolasetron mesylate and dexamethasone with or without aprepitant in preventing nausea and vomiting in patients undergoing oxaliplatin-containing chemotherapy for gastrointestinal malignancy. Antiemetic drugs may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. It is not yet known whether giving aprepitant together with dolasetron mesylate and dexamethasone is more effective than dolasetron mesylate and dexamethasone alone in preventing nausea and vomiting.

Study Overview

• Status: Terminated
• Conditions: Nausea and Vomiting; Malignant Digestive System Neoplasm
• Intervention / Treatment: Drug: Dexamethasone; Drug: Placebo; Drug: Aprepitant; Drug: Dolasetron Mesylate

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the incidence and severity of acute and delayed nausea and vomiting associated with oxaliplatin-containing regimens in patients with gastrointestinal (GI) malignancy.

II. To estimate the percent of patients who have experienced nausea and vomiting with their first or second cycle of oxaliplatin-containing regimen, and would consent to randomization to standard antiemetic therapy with or without aprepitant.

III. To obtain preliminary data on the safety and efficacy of aprepitant, in combination with dolasetron (dolasetron mesylate) and dexamethasone, in patients receiving oxaliplatin-containing regimen.

IV. To report on medication compliance with antiemetic medications (dexamethasone and aprepitant or placebo) scheduled to be taken at home on days 2 and 3 for all randomized patients (day 1 = day of treatment).

OUTLINE: Patients receive standard antiemetics comprising dolasetron mesylate orally (PO) or intravenously (IV) and dexamethasone PO or IV during course 1 of oxaliplatin-containing chemotherapy. Patients experiencing any grade 1-4 nausea and vomiting* are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dolasetron mesylate PO or IV, dexamethasone PO or IV, and aprepitant PO 1 day before chemotherapy and dexamethasone PO and aprepitant PO on days 2 and 3 after chemotherapy begins during course 2-3.

ARM II: Patients receive dolasetron mesylate and dexamethasone as in Arm I and placebo PO 1 day before chemotherapy and dexamethasone PO and placebo PO on days 2 and 3 after chemotherapy begins during courses 2-3.

In both arms, treatment continues in the absence of unacceptable toxicity.

NOTE: * Patients not developing nausea and vomiting until the second course of treatment are also randomized during courses 3 and 4 of chemotherapy.

After completion of study treatment, patients are followed up periodically.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who have a diagnosis of GI malignancy and who are scheduled to receive their initial treatment with an oxaliplatin-containing regimen in combination with 5-fluorouracil; these include combinations such as fluorouracil, oxaliplatin, and leucovorin calcium (FOLFOX), FOLFOX + bevacizumab, FOLFOX + cetuximab

• Standard antiemetic therapy with initial treatment must include the dolasetron and dexamethasone; the minimum adequate doses include either:

  • Dolasetron (Anzemet) 100mg PO/IV or 1.8mg/kg IV AND
  • Dexamethasone (Decadron) 10mg PO/IV
• Patient must agree, as part of the informed consent, to keep a journal of the episodes of nausea, vomiting, retching, and amount of rescue medications used on days 1 to 5 (day 1 = day of treatment)
• Signed informed consent

Exclusion Criteria:

• Allergy or intolerance to dolasetron and dexamethasone
• Use of another antiemetic agent (5HT3 antagonists, phenothiazines, butyrophenones, cannabinoids, metoclopramide, or corticosteroids) within 72 hours of day 1 of the study
• An episode of vomiting or retching within 24 hours before the start of the initial treatment with oxaliplatin-containing regimen
• Severe concurrent illness other than neoplasia
• Gastrointestinal obstruction or an active peptic ulcer
• Radiation therapy to the abdomen or pelvis within 1 week before or after day 1 of the study
• Absolute neutrophil count of less than 1.5 x 10^9/L (unless physician approves to proceed with chemotherapy) or
• Platelets less than 100 x 109/L (unless physician approves to proceed with chemotherapy)
• Total bilirubin > 2 x upper limits of normal
• Patients who are pregnant or breast feeding
• Patients who are non-English speaking
• Patients with cancer-induced nausea and vomiting grade 1 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I (aprepitant, dolasetron mesylate, dexamethasone); Patients receive dolasetron mesylate PO or IV, dexamethasone PO or IV, and aprepitant PO 1 day before chemotherapy and dexamethasone PO and aprepitant PO on days 2 and 3 after chemotherapy begins during course 2-3.	Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; Visumetazone; Drug: Aprepitant; Given PO; Other Names: Emend; L-754030; MK-0869; ONO-7436; Drug: Dolasetron Mesylate; Given PO or IV; Other Names: Anzemet; MDL 73,147EF
PLACEBO_COMPARATOR: Arm II (placebo, dolasetron mesylate, dexamethasone); Patients receive dolasetron mesylate and dexamethasone as in Arm I and placebo PO 1 day before chemotherapy and dexamethasone PO and placebo PO on days 2 and 3 after chemotherapy begins during courses 2-3.	Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; Visumetazone; Drug: Placebo; Given PO; Other Names: PLCB; sham therapy; Drug: Dolasetron Mesylate; Given PO or IV; Other Names: Anzemet; MDL 73,147EF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with complete response, defined as no emesis and no use of rescue medication	We will summarize the incidence, severity and time of onset of all nausea and vomiting experienced by all patients who received any oxaliplatin. The complete response rates in both arms will be calculated with 95% confidence intervals.	Within the first 24 hours of treatment (day 1)

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients who agreed to be randomized out of all patients who qualify for randomization	28 days

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Betty Chan, University of Southern California

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 19, 2006
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: September 13, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (ESTIMATE): September 15, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Nausea; Vomiting; Gastrointestinal Neoplasms; Digestive System Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Aprepitant; Ichthammol; Dolasetron
• Other Study ID Numbers: 3C-06-1 (OTHER: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2012-01740 (REGISTRY: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No