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

• Acute, Delayed and Overall Total Protection [ Time Frame: Up to 5 days (first 5 days of the first cycle of chemotherapy) ] [ Designated as safety issue: No ]
  Total protection is defined as 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.
• Complete response and Complete Protection for the acute, delayed, and overall periods [ Time Frame: Up to 5 days (first 5 days following first cycle of chemotherapy) ] [ Designated as safety issue: No ]
  Complete response is defined as vomiting episodes with rescue medication, and 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.

• 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

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.

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 intravenous (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).

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

• Drug: dexamethasone
  10 mg IV 30 minutes prior to administration of chemotherapy
• Drug: dronabinol
  5 mg tablet by mouth three times a day beginning 30 minutes before chemotherapy
• Drug: palonosetron hydrochloride
  0.25 mg IV 30 minutes prior to administration of chemotherapy
• Other: placebo
  1 tablet by mouth three times a day beginning 30 minutes before chemotherapy

• Experimental: Arm I: Palonosetron, Dexamethasone + Dronabinol
  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.
  Interventions:

  • Drug: dexamethasone
  • Drug: dronabinol
  • Drug: palonosetron hydrochloride
• Active Comparator: Arm II: Palonosetron + Dexamethasone
  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.
  Interventions:

  • Drug: dexamethasone
  • Drug: palonosetron hydrochloride
  • Other: placebo

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumors

• Receiving a moderately emetogenic chemotherapy regimen for the first time

  • Patients may be chemotherapy naive or 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 ≤ 1,500 mg/m^2 intravenous (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 central nervous system (CNS) tumor (including those with uncontrolled seizures)

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• White Blood Count (WBC) ≥ 3,000/mm^3
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 * upper limit of normal (ULN)
• Bilirubin ≤ 2.5 * ULN
• Transaminases ≤ 2.5 * 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, hexamethylmelamine, mechlorethamine, procarbazine) [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