Palonosetron and Dexamethasone With or Without Dronabinol in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy For Cancer

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical research study is to learn if adding dronabinol in combination with the standard of care (dexamethasone and palonosetron) can better help to control nausea and vomiting in patients receiving chemotherapy. The safety of the drug combinations will also be studied.

Detailed Description
-----------------
The Study Drugs: Dronabinol and palonosetron are both designed to help prevent nausea and vomiting in patients who are receiving chemotherapy. Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body. Dexamethasone is often given to MM patients in combination with other chemotherapy to treat cancer. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. If you are in Group 1, you will take dronabinol, dexamethasone, and palonosetron. If you are in Group 2, you will take a placebo, dexamethasone, and palonosetron. A placebo is a substance that looks like the study drug but has no active ingredients. You will have an equal chance of being assigned to either group. Neither you nor your doctor can choose the group you will be in. During the study, you and the study staff will not know which group you are in. However, if needed for your safety, the study staff will be able to find out which group you are in. After the last study participant completes their study therapy, you and the study staff will find out which group you were in. Study Drug Administration: On Day 1 (the day that you receive chemotherapy), you will take a dronabinol/placebo pill by mouth every 8 hours (if possible). If you cannot take the pill every 8 hours, you should try to space out the doses evenly. Your first dronabinol/placebo pill on Day 1 will be 30 minutes before chemotherapy. You will also receive dexamethasone and palonosetron by vein 30 minutes before you receive chemotherapy. On Days 2-6, you will take dronabinol/placebo 3 times a day. You should take each pill every 8 hours (if possible). If you cannot take them every 8 hours, you should try to space out the doses evenly. Study Diary: You will complete a study diary on Days 1-6. In this diary you will answer questions about nausea and vomiting. Study Visits: You will have a study visit on Day 8 and again sometime during Days 14-28. At both visits, you will be asked if you have experienced any side effects. You should return your study diary to the clinic at both visits. At the visit during Days 14-28, you will also have a physical exam. Length of Study: You will be on study for 30 days. You will be taken off study early if the nausea and vomiting do not improve or intolerable side effects occur. This is an investigational study. Dronabinol and palonosetron are both FDA approved and commercially available to prevent nausea and vomiting that may occur from chemotherapy. Dexamethasone is FDA approved and commercially available for the prevention of side effects related to chemotherapy. The combination of these drugs to prevent nausea and vomiting is investigational. Up to 200 patients will take part in this multicenter study. Up to 200 will be enrolled at M. D. Anderson.

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled Trial of Palonosetron/Dexamethasone With or Without Dronabinol for the Prevention of Chemotherapy-Induced Nausea and Vomiting After Moderately Emetogenic Chemotherapy

Conditions
-----------------
Chemotherapy-induced Nausea and Vomiting, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: dexamethasone
* Drug: dronabinol
* Drug: palonosetron hydrochloride
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically documented solid tumor Receiving moderately emetogenic chemotherapy for the first time: Patients may be chemotherapy naive, or patients may have previously received a mildly emetogenic agent (such as a taxane) if no nausea/vomiting was experienced with that chemotherapy Scheduled to receive cyclophosphamide </= 1500 mg/m^2 IV and/or doxorubicin >/= 40 mg/m^2 IV given as single doses on Day 1. Patients on combination regimens with these agents are eligible Age >/= 18 years Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Adequate organ reserve as follows: 1) Hematologic - white blood cell count (WBC) >/= 3000/microL, AGC >/= 1500/microL, platelet >/= 100,000/microL; 2) Renal - Creatinine </= 1.5 times upper limit of normal; 3) Hepatic - Bilirubin and transaminases </= 2.5 times upper limit of normal The effects of the three-drug regimen on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Negative qualitative B-human chorionic gonadotropin (HCG) (pregnancy test) Signed informed consent Exclusion Criteria: Scheduled to receive highly emetogenic chemotherapy (Hesketh Level 5 - such as cisplatin, streptozotocin, dacarbazine, carmustine, hexamethylmelamine, mechlorethamine, procarbazine) during the study period Scheduled to receive moderately emetogenic chemotherapy (Hesketh Level 3-4) after Day 1 of the study period Experienced nausea and/or vomiting with prior administration of chemotherapy Prior moderately or highly emetogenic chemotherapy: Patients may have previously received a mildly emetogenic agent (such as a taxane) if no nausea/vomiting was experienced with that chemotherapy Scheduled to receive cranial, abdominal, or pelvic radiation therapy during the study period Treatment with any investigational agent within 30 days of randomization Scheduled to receive treatment during the study period with other potential or known antiemetic agents. Chronically used benzodiazepines may be continued as a single nightly dose for sleep. Scheduled to receive corticosteroid treatment other than the study drug dose during the study period Uncontrolled primary or metastatic CNS tumor (including those with uncontrolled seizures) Other physical causes for nausea or vomiting (such as bowel obstruction) not related to chemotherapy administration Recent history of unexplained nausea or vomiting or history of frequent nausea or vomiting Active bacterial or fungal infection for which administration of a corticosteroid would be contraindicated Hypersensitivity to any of the study agents Sensitivity to sesame oil Planned simultaneous administration of any other investigational agents Pregnant or nursing women Previous poor tolerance of cannabinoids Habitual cannabinoid use or unwillingness to avoid the use of marijuana during the study period Previous use of dronabinol or nabilone

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: Palonosetron, Dexamethasone + Dronabinol<br>Palonosetron hydrochloride intravenous (IV) and dexamethasone IV 30 minutes before chemotherapy administration on day 1, and oral dronabinol 3 times a day for 5 days beginning 30 minutes before chemotherapy administration on day 1. | Drug: dexamethasone<br>* 10 mg IV 30 minutes prior to administration of chemotherapy<br>Drug: dronabinol<br>* 5 mg tablet by mouth three times a day beginning 30 minutes before chemotherapy<br>Drug: palonosetron hydrochloride<br>* 0.25 mg IV 30 minutes prior to administration of chemotherapy<br>|
| Active Comparator: Arm II: Palonosetron + Dexamethasone<br>Palonosetron hydrochloride and dexamethasone as in arm I, and oral placebo 3 times a day for 5 days beginning 30 minutes before chemotherapy on day 1. | Drug: dexamethasone<br>* 10 mg IV 30 minutes prior to administration of chemotherapy<br>Drug: palonosetron hydrochloride<br>* 0.25 mg IV 30 minutes prior to administration of chemotherapy<br>Other: placebo<br>* 1 tablet by mouth three times a day beginning 30 minutes before chemotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Total Protection in the Acute, Delayed and Overall Periods | Total protection is defined as no vomiting, no rescue therapy, and no nausea as indicated by responses to the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire. Data to be recorded in the study diary during the 5-day study period. The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. | 5 Days (first 5 days of the first cycle of chemotherapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Protection for the Acute, Delayed, and Overall Periods | Complete Protection is no vomiting, no rescue therapy, and no nausea evaluated for the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire. The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. | Up to 5 days (first 5 days following first cycle of chemotherapy) | 
| Number of Participants With Complete Response for the Acute, Delayed, and Overall Periods | Complete response is defined as vomiting episodes with rescue medication evaluated for the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire. The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. | Up to 5 days (first 5 days following first cycle of chemotherapy) | 
| Number of Participants With Vomiting for the Acute, Delayed and Overall Periods | Number of Participants with Vomiting Acute, Delayed and Overall. Evaluated for the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire. The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. | 5 Days (first 5 days of the first cycle of chemotherapy) | 
| Number of Participants With Nausea for the Acute, Delayed and Overall Periods | Number of Participants with Nausea for the Acute, Delayed and Overall Periods. Evaluated for the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire. The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. | 5 Days (first 5 days of the first cycle of chemotherapy) | 
| Number of Participants With Nausea and Vomiting for the Acute, Delayed and Overall Periods | Number of Participants With Nausea and Vomiting for the Acute, Delayed and Overall Periods. Evaluated for the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire. The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. | 5 Days (first 5 days of the first cycle of chemotherapy) | 
| Number of Participants Received Rescue Medication in the Acute, Delayed and Overall Periods | The assessment measures in detail the occurrence, duration, and severity of post-chemotherapy nausea and emesis using a 10-point Likert-type scale ranging from 0 (none) to 10 (as bad as it could be) if nausea or vomiting is present. The first section asks the patient to record presence and severity of nausea during the last 24 hours. The second section asks the patient to record vomiting episodes during the last 24 hours. The third section asks if the patient took medication for nausea or vomiting during the last 24 hours and asks how useful the treatment for nausea or vomiting was. The fourth section screens for toxicity by asking about side effects and problems experienced during the last 24 hours. Use of rescue antiemetic medication and adverse events also assessed and documented. | 5 Days (first 5 days of the first cycle of chemotherapy) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nausea and vomiting, unspecified adult solid tumor, Palonosetron, Dexamethasone