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

Condition(s) targeted: Nausea and Vomiting; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: dexamethasone (Drug); dronabinol (Drug); palonosetron hydrochloride (Drug); placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Steven M. Grunberg, MD, Study Chair, Affiliation: Vermont Cancer Center at University of Vermont
Michael J. Fisch, MD, MPH, FACP, Affiliation: M.D. Anderson Cancer Center

RATIONALE: Antiemetic drugs, such as dexamethasone, palonosetron, and dronabinol may help lessen or prevent nausea and vomiting caused by chemotherapy. It is not yet known whether giving dronabinol together with palonosetron and dexamethasone is more effective than giving palonosetron and dexamethasone in preventing nausea and vomiting caused by chemotherapy.

PURPOSE: This randomized phase III trial is studying giving dronabinol together with palonosetron and dexamethasone to see how well they work compared to giving palonosetron and dexamethasone alone in preventing nausea and vomiting in patients undergoing chemotherapy for cancer.

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

Study design: Supportive Care, Randomized, Double-Blind, Placebo Control

Primary outcome: Total protection (i.e., no vomiting, no rescue therapy, and no nausea as indicated by responses to the Daily Assessment of Nausea and Vomiting questionnaire during the overall [0-120 hour] period)

Secondary outcome:

No vomiting, no significant nausea, and no nausea evaluated for the acute (0-24 hour), delayed (24-120 hour), and overall (0-120 hour) periods

Complete protection and complete response for the acute, delayed, and overall periods

Detailed description: OBJECTIVES:

- To determine whether dronabinol can add significantly to the antiemetic protection

provided by a standard palonosetron hydrochloride and dexamethasone regimen for patients receiving moderately emetogenic chemotherapy.

- To determine the tolerability of dronabinol when added to a regimen of dexamethasone and

palonosetron hydrochloride administered for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy.

- To determine tolerability, in terms of treatment-limiting toxicities, observed with the

three-drug combination.

OUTLINE: This is a multicenter study. Patients are stratified according to study center. Patients receive scheduled chemotherapy (cyclophosphamide and/or doxorubicin hydrochloride) beginning on day 1. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive palonosetron hydrochloride IV and dexamethasone IV 30 minutes

before chemotherapy administration on day 1. Patients also receive oral dronabinol 3 times a day for 5 days beginning 30 minutes before chemotherapy administration on day 1.

- Arm II: Patients receive palonosetron hydrochloride and dexamethasone as in arm I.

Patients also receive an oral placebo 3 times a day for 5 days beginning 30 minutes before chemotherapy on day 1.

In both arms, treatment continues in the absence of nausea or vomiting within 24 hours after initiation of chemotherapy.

Patients complete a Daily Assessment of Nausea and Vomiting questionnaire after the administration of chemotherapy on days 1-5.

Patients are followed at the completion of course 1 of chemotherapy (days 14-28).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed solid tumors

- Receiving a moderately emetogenic chemotherapy regimen for the first time

- Scheduled to receive cyclophosphamide ≤ 1,500 mg/m^2 IV and/or doxorubicin

hydrochloride ≥ 40 mg/m^2 IV given as single doses on day 1 of chemotherapy regimen

- Patients on combination regimens with these agents are eligible

- No concurrent moderately emetogenic chemotherapy (Hesketh Level 3-4) after day 1

of the study period

- Hesketh Level 1-2 chemotherapy on days 2-5 allowed

- No other physical causes for nausea or vomiting not related to chemotherapy

administration (i. e., bowel obstruction)

- No recent history of unexplained nausea or vomiting or history of frequent nausea or

vomiting

- No uncontrolled primary or metastatic CNS tumor (including those with uncontrolled

seizures)

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- WBC ≥ 3,000/mm^3

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 1. 5 x upper limit of normal (ULN)

- Bilirubin ≤ 2. 5 x ULN

- Transaminases ≤ 2. 5 x ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active bacterial or fungal infection for which administration of a corticosteroid

would be contraindicated

- No hypersensitivity to any of the study agents

- No sensitivity to sesame oil

- No previous poor tolerance of cannabinoids

- No habitual cannabinoid use or unwillingness to avoid the use of marijuana during the

study period

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 30 days since prior treatment with any investigational agent

- No prior chemotherapy

- No prior dronabinol or nabilone

- No concurrent highly emetogenic chemotherapy (i. e., cisplatin, streptozotocin,

dacarbazine, carmustine, altretamine, mechlorethamine hydrochloride, or procarbazine hydrochloride [Hesketh Level 5])

- No concurrent cranial, abdominal, or pelvic radiotherapy

- No concurrent corticosteroid treatment other than the study drug dose

- No other concurrent potential or known prophylactic antiemetic agents

- Chronically used benzodiazepines may be continued as a single nightly dose for

sleep

- No other concurrent investigational agents

University of Texas M.D. Anderson CCOP Research Base, Houston, Texas 77030-4009, United States; Recruiting
Michael J. Fisch, MD, MPH, FACP, Phone: 713-563-9905

Vermont Cancer Center at University of Vermont, Burlington, Vermont 05405, United States; Recruiting
Steven M. Grunberg, MD, Phone: 802-656-5457, Email: steven.grunberg@uvm.edu

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2008
Last updated: October 28, 2008