Palonosetron Hydrochloride in Preventing Nausea and Vomiting Caused by Radiation Therapy in Patients With Primary Abdominal Cancer

Study Overview
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Brief Summary
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RATIONALE: Palonosetron hydrochloride may prevent nausea and vomiting caused by radiation therapy. It is not yet known whether palonosetron hydrochloride is more effective than a placebo in preventing nausea and vomiting. PURPOSE: This randomized phase II trial is studying the side effects of palonosetron hydrochloride and to see how well it works in preventing nausea and vomiting caused by radiation therapy in patients with primary abdominal cancer.

Detailed Description
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OBJECTIVES: Evaluate the rate of complete responses, defined as no vomiting and no nausea, in patients with primary gastrointestinal and/or retroperitoneal sarcomas treated with two different dosing schedules of palonosetron hydrochloride during abdominal radiotherapy as part of their cancer treatment. Determine the tolerability of palonosetron hydrochloride vs placebo in these patients. Validate patient diaries for assessing nausea and vomiting by comparing with alternative methods for measuring nausea and vomiting in order to determine the optimal approach for future studies. OUTLINE: Patients are stratified according to planned radiotherapy duration (< 5 weeks vs ≥ 5 weeks), planned concurrent fluorouracil ( yes vs no), and gender. Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive palonosetron hydrochloride IV on day 1. Arm II: Patients receive palonosetron hydrochloride IV on days 1 and 4. Arm III: Patients receive placebo IV on day 1. Arm IV: Patients receive placebo IV on days 1 and 4. In all arms, courses repeat weekly during radiotherapy in the absence of disease progression or unacceptable toxicity. Patients complete nausea and vomiting questionnaires and diaries at baseline and daily during radiotherapy. Patients also complete symptom experience diaries weekly during radiotherapy.

Official Title
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A Pilot Phase II, Randomized, Double Blind Trial of Palonosetron Versus Placebo to Prevent Radiation Therapy Induced Nausea and Vomiting

Conditions
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Anal Cancer, Carcinoma of the Appendix, Colorectal Cancer, Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Gastric Cancer, Gastrointestinal Carcinoid Tumor, Liver Cancer, Nausea and Vomiting, Pancreatic Cancer, Primary Peritoneal Cavity Cancer, Small Intestine Cancer

Intervention / Treatment
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* Drug: palonosetron hydrochloride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of primary gastrointestinal and/or retroperitoneal sarcoma Scheduled to undergo ≥ 3000 cGy or ≥ 3 weeks of external beam radiation to the abdomen Radiotherapy fields to extend between T11 and L3, and of a size ≥ 100 cm^2 No brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Negative pregnancy test Not pregnant or nursing Fertile patients must use effective contraception Able to complete questionnaire(s) alone or with assistance Willing to return to NCCTG enrolling institution for follow-up Able to reliably take oral medication (for purposes of rescue medication) No hypersensitivity to palonosetron hydrochloride or other selective 5-HT3 receptor antagonists No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for study entry or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens No nausea ≤ 48 hours prior to study enrollment No history of dystonic reactions to prochlorperazine or haloperidol or related agents PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 7 days since prior agents known to have significant effects on emesis, including the following: Ondansetron Sedating antihistamines Antipsychotics Cannabinoids Corticosteroids Metoclopramide Narcotic analgesics Benzodiazepines More than 7 days since prior chemotherapy other than fluorouracil or capecitabine used as a radiosensitizer More than 7 days since of prior cetuximab More than 7 days since prior and no concurrent oral steroids No prior palonosetron hydrochloride

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive palonosetron hydrochloride IV on day 1. | Drug: palonosetron hydrochloride<br>* Given IV<br>|
| Experimental: Arm II<br>Patients receive palonosetron hydrochloride IV on days 1 and 4. | Drug: palonosetron hydrochloride<br>* Given IV<br>|
| Placebo Comparator: Arm III<br>Patients receive placebo IV on day 1. | Other: placebo<br>* Given IV<br>|
| Placebo Comparator: Arm IV<br>Patients receive placebo IV on days 1 and 4. | Other: placebo<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (no Episodes of Nausea or Vomiting) |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Treatment Failure, Defined as a Single Episode of Vomiting, Daily Nausea Score of Moderate or Greater, or Taking ≥ 3 Prochlorperazine or Haloperidol Tablets Per Day |  | Up to 2 years | 
| Proportion of Patients Reporting Treatment Failure |  | Up to 2 years | 
| Tolerability and Adverse Events as Assessed by NCI CTC v 3.0 |  | Up to 2 years | 
| Average Level of Nausea Reported and the Proportion of Patients Experiencing a Complete Response Independent of Treatment Arm |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea and vomiting, gastrointestinal carcinoid tumor, anal cancer, carcinoma of the appendix, colon cancer, rectal cancer, extrahepatic bile duct cancer, gallbladder cancer, gastric cancer, liver and intrahepatic biliary tract cancer, pancreatic cancer, small intestine cancer, primary peritoneal cavity cancer