Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy

Phase II Study of Rolapitant Plus Olanzapine, Palonosetron, and Dexamethasone in Patients With Germ Cell Tumors Undergoing 5-day Cisplatin-based Chemotherapy.

Phase II study of Rolapitant plus Olanzapine, Palonosetron, and Dexamethasone in patients with germ cell tumors undergoing 5-day Cisplatin-based chemotherapy

Study Overview

• Status: Withdrawn
• Conditions: Germ Cell Tumor
• Intervention / Treatment: Drug: Rolapitant; Drug: Palonosetron; Drug: Olanzapine; Drug: Dexamethasone

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 15 years at the time of consent.
• Must be able to take oral medications (swallow pills)
• ECOG Performance Status of 0-2 within 14 days prior to registration.
• Histological or serological confirmation of germ cell tumor planning on receiving a standard 5 day cisplatin based chemotherapy regimen.
• Patients must have had no nausea or vomiting for 24 hours and no antiemetic use for 72 hours prior to starting protocol therapy.
• No active central nervous system (CNS) metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis. A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
• Prior cancer treatments are not allowed. Patients have to be chemotherapy naïve.
• Absolute Neutrophil Count (ANC) ≥ 1 K/mm3
• Hemoglobin (Hgb) ≥ 10 g/dL
• Platelets (Plt) ≥ 100 K/mm3
• Creatinine ≤ 2 mg/dL
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• No concurrent use of thioridazine or pimozide. No use of agents expected to induce the metabolism of rolapitant which include: Rifampin, Rifabutin, Phenytoin, Carbamazepine, and Barbiturates.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
• Patients and their partners must agree to use a highly effective method of birth control from the signing of the informed consent form until 90 days following the last dose of rolapitant.

Exclusion Criteria:

• Any untreated central nervous system (CNS) metastases.
• Treatment with any investigational drug within 30 days prior to registration.
• Concurrent participation in a clinical trial which involves another investigational agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rolapitant; Rolapitant plus Olanzapine, Palonosetron, and Dexamethasone	Drug: Rolapitant; Rolapitant 180mg PO, Days 1 and 5; Other Names: Varubi; Drug: Palonosetron; Palonosetron 0.25 mg IV, Days 1,3, and 5.; Other Names: Aloxi; Drug: Olanzapine; Olanzapine 10 mg PO PM, Days 2,3,4,5,6-8; Other Names: Zyprexa; Drug: Dexamethasone; Dexamethasone 20 mg AM, Days 1,2 and 3; Other Names: steroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	Determine the complete response (CR) rate defined as no emesis and no use of rescue medications in germ cell tumor patients treated with rolapitant plus Olanzapine in combination with palonosetron a 5HT3RA and dexamethasone on Cycle 1 Day 1 through Day 8	8 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate: Acute Phase	Determine the CR rate in the acute phase (Days 1-5) defined as no emesis and no use of rescue medications in germ cell tumor patients treated with rolapitant plus Olanzapine in combination with palonosetron a 5HT3RA and dexamethasone on Cycle 1 Day 1 through Day 5	5 Days
Complete Response Rate: Delayed Phase	Determine the CR rate in the delayed phase (Days 6-8) defined as no emesis and no use of rescue medications in germ cell tumor patients treated with rolapitant plus Olanzapine in combination with palonosetron a 5HT3RA and dexamethasone on Cycle 1 Day 6 through Day 8	2 Days
Frequency, intensity, and duration of nausea	Determine the frequency, intensity and duration of nausea on Days 1-8 in Cycle 1. The frequency, intensity and duration of nausea will be captured via daily self-assessment patient logs.	8 Days
Frequency of vomiting or retching.	Determine the frequency, intensity and duration of vomiting or retching on Days 1-8 in Cycle 1. The frequency of vomiting and retching will be captured via daily self-assessment patient logs.	8 Days
Intensity of Vomiting or retching.	Determine the intensity of vomiting or retching on Days 1-8 in Cycle 1. The intensity of vomiting and retching will be captured via daily self-assessment patient logs.	8 Days
Duration of Vomiting or retching	Determine the duration of vomiting or retching on Days 1-8 in Cycle 1. The duration of vomiting and retching will be captured via daily self-assessment patient logs.	8 Days
Rate of no nausea	Determine the rate of no nausea defined as < 5mm on a 0-100mm visual analog scale (VAS) on Days 1-5 and Days 6-8 on Cycle 1	8 Days
Use of rescue medications	Describe the use of rescue medications as defined in the protocol	8 Days
Assess adverse events of regimen using CTCAE v4.	Safety and toxicity will be assessed using CTCAE v4	8 Days

Collaborators and Investigators

• Sponsor: Costantine Albany
• Collaborators: Tesaro, Inc.
• Investigators: Principal Investigator: Costantine Albany, MD, Indiana University Melvin and Bren Simon Cancer Center

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2018
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): May 22, 2019
• Last Update Submitted That Met QC Criteria: May 21, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Olanzapine; Palonosetron; Rolapitant
• Other Study ID Numbers: HCRN GU16-254

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes