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

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

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.

Study Overview

• Status: Terminated
• Conditions: Locally Advanced Sarcoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Ifosfamide; Other: Questionnaire Administration; Drug: Vincristine Sulfate; Drug: Doxorubicin; Drug: Mesna; Drug: Dexamethasone; Drug: Ondansetron; Drug: Rolapitant Hydrochloride; Drug: Fosaprepitant Dimeglumine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (rolapitant hydrochloride); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942; Asta Z-4942; Cyfos; Holoxan; Holoxane; Ifex; IFO; IFO-Cell; Ifolem; Ifomida; Ifomide; Ifosfamidum; Ifoxan; IFX; Iphosphamid; Iphosphamide; Iso-Endoxan; Isoendoxan; Isophosphamide; Mitoxana; MJF 9325; MJF-9325; Naxamide; Seromida; Tronoxal; Z 4942; Z-4942; Other: Questionnaire Administration; Ancillary studies; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Drug: Mesna; Given IV; Other Names: Mesnex; 2-Mercaptoethanesulfonate, Sodium Salt; Ausobronc; D-7093; Filesna; Mercaptoethane Sulfonate; Mercaptoethanesulfonate; Mesnil; Mesnum; Mexan; Mistabron; Mistabronco; Mitexan; Mucofluid; Mucolene; UCB 3983; Uromitexan; Ziken; Drug: Dexamethasone; Given IV; Other Names: Decadron; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Ondansetron; Given IV; Other Names: Zofran ODT; Zuplenz; Drug: Rolapitant Hydrochloride; Given PO; Other Names: Varubi; Rolapitant HCl; Rolapitant Hydrochloride Monohydrate; Rolapitant Monohydrochloride Monohydrate; SCH-619734; SCH619734
Active Comparator: Arm II (fosaprepitant dimeglumine); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942; Asta Z-4942; Cyfos; Holoxan; Holoxane; Ifex; IFO; IFO-Cell; Ifolem; Ifomida; Ifomide; Ifosfamidum; Ifoxan; IFX; Iphosphamid; Iphosphamide; Iso-Endoxan; Isoendoxan; Isophosphamide; Mitoxana; MJF 9325; MJF-9325; Naxamide; Seromida; Tronoxal; Z 4942; Z-4942; Other: Questionnaire Administration; Ancillary studies; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Drug: Mesna; Given IV; Other Names: Mesnex; 2-Mercaptoethanesulfonate, Sodium Salt; Ausobronc; D-7093; Filesna; Mercaptoethane Sulfonate; Mercaptoethanesulfonate; Mesnil; Mesnum; Mexan; Mistabron; Mistabronco; Mitexan; Mucofluid; Mucolene; UCB 3983; Uromitexan; Ziken; Drug: Dexamethasone; Given IV; Other Names: Decadron; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Ondansetron; Given IV; Other Names: Zofran ODT; Zuplenz; Drug: Fosaprepitant Dimeglumine; Given IV; Other Names: MK-0517; Emend for Injection; L-785,298

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Saroj Vadhan, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2016
• Primary Completion (Actual): July 10, 2020
• Study Completion (Actual): July 10, 2020

Study Registration Dates

• First Submitted: April 4, 2016
• First Submitted That Met QC Criteria: April 4, 2016
• First Posted (Estimate): April 8, 2016

Study Record Updates

• Last Update Posted (Actual): August 9, 2021
• Last Update Submitted That Met QC Criteria: August 5, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Signs and Symptoms, Digestive; Sarcoma; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antibiotics, Antineoplastic; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Vincristine; Daunorubicin; Ondansetron; Aprepitant; Fosaprepitant; Mesna; Rolapitant
• Other Study ID Numbers: 2015-0587 (Other Identifier: M D Anderson Cancer Center); NCI-2016-00801 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No