Rolapitant Hydrochloride in Preventing Nausea/Vomiting in Patients With Sarcoma Receiving Chemotherapy

Study Overview
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Brief Summary
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This randomized phase II trial studies how well rolapitant hydrochloride works in preventing nausea/vomiting in patients with sarcoma receiving chemotherapy. Antiemetic drugs, such as rolapitant hydrochloride, may help control or prevent nausea and vomiting in patients treated with chemotherapy.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the effect of rolapitant hydrochloride (rolapitant) on nausea/vomiting in patients with sarcoma receiving multi-day highly emetogenic chemotherapy (HEC) regimen of doxorubicin and ifosfamide (AI). SECONDARY OBJECTIVES: I. To evaluate the toxicity of rolapitant in patients receiving AI regimen. II. To evaluate the effects of rolapitant on patient reported outcomes. OUTLINE: PART I: Patients receive dexamethasone intravenously (IV) daily and ondansetron IV on days 1-5, and rolapitant hydrochloride orally (PO) on day 1. PART II: Patients are randomized to 1 of 2 arms. ARM I: Patients receive treatment as in part I. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive dexamethasone IV and ondansetron IV on days 1-5, and fosaprepitant dimeglumine IV over 30 minutes on days 1 of cycle 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY: All patients receive doxorubicin IV over 72 hours, mesna IV, and ifosfamide IV over 3 hours on days 1-4 or 1-5. Patients with sarcomas of small cell histology receive vincristine sulfate IV on day 1. Cycles repeat every 3 weeks following blood count and patient recovery from any acute toxicities.

Official Title
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Effects of Rolapitant on Nausea/Vomiting in Patients With Sarcoma Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC) With Doxorubicin and Ifosfamide Regimen (AI)

Conditions
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Locally Advanced Sarcoma

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Doxorubicin
* Drug: Fosaprepitant Dimeglumine
* Drug: Ifosfamide
* Other: Laboratory Biomarker Analysis
* Drug: Mesna
* Drug: Ondansetron
* Other: Questionnaire Administration
* Drug: Rolapitant Hydrochloride
* Drug: Vincristine Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with doxorubicin plus ifosfamide (AI) or AI and vincristine (VAI) is indicated Patient must have an estimated life expectancy >= 4 months in the opinion of the investigators Male and females of child bearing potential must use acceptable methods of birth control which include oral contraceptives, spermicide with either a condom, diaphragm or cervical cap, use of an intrauterine device (IUD) or abstinence Female patients must have a negative pregnancy test at screening Female patients of childbearing potential must agree to use an acceptable method of birth control (excluding hormonal birth control methods) for 72 hours prior to admission and to continue its use during the study and for at least 30 days after the final dose Male patients must agree to use an acceptable form of birth control from study day 1 through at least 30 days after the final dose Absolute neutrophil count (ANC) > 1500/mm^3 Platelet count > 100,000/mm^3 Serum creatinine < 1.5 mg/dL Serum bilirubin count < 1.5 x upper limit normal (ULN) Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) < 2.5 x ULN; for subjects with known liver metastases < 5 x ULN Karnofsky performance status > 60% Signed informed consent form Patients are required to read and understand English to comply with protocol requirements Exclusion Criteria: Any current treatment, medical history, or uncontrolled condition, other than malignancy, (e.g., alcoholism or signs of alcohol abuse, seizure disorder, medical or psychiatric condition) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject Patient has a known hypersensitivity to the administration of any prescribed oral or intravenous study medication or metabolite, including but not limited to, a history of hypersensitivity to the drugs or their components, severe renal impairment, severe bone marrow suppression, or systemic infection Patient is a woman with a positive urine or serum pregnancy test within 3 days prior to study drug administration, is breast-feeding, or is planning to conceive children within the projected duration of the study treatment Patient has taken the anti-emetic agents within the last 48 hours prior to the start of treatment with study drug: 5-hydroxytryptamine (HT)3 antagonists (ondansetron, granisetron, dolasetron, tropisetron, etc.); palonosetron is not permitted within 7 days prior to administration of investigational product Phenothiazines (prochlorperazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine, etc.) Benzamides (metoclopramide, alizapride, etc.) Domperidone Cannabinoids Neurokinin (NK)1 antagonist (aprepitant) Benzodiazepines (lorazepam, alprazolam, etc) Herbal medications or preparations in doses designed to ameliorate nausea or emesis Patient has received systemic corticosteroids or sedative antihistamines (dimenhydrinate, diphenhydramine, etc.) within 72 hours of day 1 of the study except as premedication for chemotherapy (e.g., taxanes); subjects who are receiving inhaled steroids for respiratory conditions or topical steroids for skin disorders can be enrolled Patient has symptomatic primary or metastatic central nervous system (CNS) disease Patient has ongoing vomiting, retching, dry heaves, or clinically significant nausea caused by any etiology, or has had such symptoms within 24 hours prior to the start of day 1 of the study intervention, or has a history of anticipatory nausea and vomiting Patient must not have been dosed with test drug or blinded study drug in another investigational study within 30 days or 5 half-lives of the biologic activity of the test drug, whichever is longer, before the time of first study dose Patient who is participating in any investigational agent that is not Food and Drug Administration (FDA)-approved Patient has uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia or hypertension, or acute myocardial infarction within 3 months Prior surgery or radiotherapy (RT) within 2 weeks of study entry Psychological, social, familial, or geographical reasons that would prevent scheduled visits and follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (rolapitant hydrochloride)<br>Patients receive treatment as in part I. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY: All patients receive doxorubicin IV over 72 hours, mesna IV, and ifosfamide IV over 3 hours on days 1-4 or 1-5. Patients with sarcomas of small cell histology receive vincristine sulfate IV on day 1. Cycles repeat every 3 weeks following blood count and patient recovery from any acute toxicities. | Drug: Dexamethasone<br>* Given IV<br>* Other names: ZoDex;Drug: Doxorubicin<br>* Given IV<br>* Other names: Hydroxyldaunorubicin;Drug: Ifosfamide<br>* Given IV<br>* Other names: Z-4942;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Mesna<br>* Given IV<br>* Other names: Ziken;Drug: Ondansetron<br>* Given IV<br>* Other names: Zuplenz;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Rolapitant Hydrochloride<br>* Given PO<br>* Other names: Varubi;Drug: Vincristine Sulfate<br>* Given IV<br>* Other names: Vincristine, sulfate;|
| Active Comparator: Arm II (fosaprepitant dimeglumine)<br>Patients receive dexamethasone IV and ondansetron IV on days 1-5, and fosaprepitant dimeglumine IV over 30 minutes on days 1 of cycle 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY: All patients receive doxorubicin IV over 72 hours, mesna IV, and ifosfamide IV over 3 hours on days 1-4 or 1-5. Patients with sarcomas of small cell histology receive vincristine sulfate IV on day 1. Cycles repeat every 3 weeks following blood count and patient recovery from any acute toxicities. | Drug: Dexamethasone<br>* Given IV<br>* Other names: ZoDex;Drug: Doxorubicin<br>* Given IV<br>* Other names: Hydroxyldaunorubicin;Drug: Fosaprepitant Dimeglumine<br>* Given IV<br>* Other names: MK-0517;Drug: Ifosfamide<br>* Given IV<br>* Other names: Z-4942;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Mesna<br>* Given IV<br>* Other names: Ziken;Drug: Ondansetron<br>* Given IV<br>* Other names: Zuplenz;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Vincristine Sulfate<br>* Given IV<br>* Other names: Vincristine, sulfate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Response (CR) of Rolapitant Hydrochloride Administered as a Single-dose | Complete response (CR) no emetic episodes and no rescue medications. | Days 1-10 |