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Study Assessing Fosaprepitant in Advanced NSCLC Patients Treated With Carboplatin Based Chemotherapy

Primary Purpose

Non-small Cell Lung Cancer, Vomiting, Nausea

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FOSAPREPITANT (Emend)
Placebo
Sponsored by
Ajeet Gajra
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring EMEND for Injection, 5HT-3, Fosaprepitant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient age > 18 years and able to sign informed consent.
  • ECOG PS 0-2
  • Patients with stage IV or recurrent NSCLC being treated with carboplatin based regimen with palliative intent.
  • Acceptable chemotherapy regimens include:

  • Carboplatin (AUC of 5 OR 6) q 21 days with:

    • Paclitaxel Q 21 days OR
    • Docetaxel Q 21 days OR
    • Pemetrexed Q 21 days (non-squamous histology with Vitamin B12 and folate supplementation) OR
    • Gemcitabine administered days 1 and 8 Q 21 days OR
    • Vinorelbine administered days 1 and 8 Q 21 days
  • The addition of bevacizumab to chemotherapy is permitted where indicated and clinically appropriate.
  • Patients who have received prior adjuvant chemotherapy for lung cancer ( > 1 year prior) and have recurred are eligible if it has been > 1 year since completion of adjuvant chemotherapy.
  • Patients who have been treated for locally advanced lung cancer with concurrent chemoradiation but completed such therapy > 1 year ago are eligible provided they meet all other inclusion criteria.
  • Patients who have received prior adjuvant chemotherapy for lung cancer ( > 1 year prior) and have recurred are eligible if it has been > 1 year since completion of adjuvant chemotherapy.
  • Patients who have been treated for locally advanced lung cancer with concurrent chemoradiation but completed such therapy > 1 year ago are eligible provided they meet all other inclusion criteria.
  • Laboratory parameters:
  • Serum creatinine < 2.0 and
  • AST, ALT < 3 time the upper limit of normal
  • Platelet count ≥ 100,00/cumm
  • ANC ≥ 1500/ cumm on day of therapy (day # 1 of the cycle)
  • Hemoglobin > 8.0 g/dl

Exclusion Criteria:

  • History of allergic reaction to aprepitant or fosaprepitant
  • Use of other investigational agents concurrently with chemotherapy
  • Uncontrolled systemic hypertension with SBP > 180 and/ or DBP> 110
  • Concurrent use of pimozide, terfenadine, astemizole, or cisapride (fosaprepitatnt is a dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). If used concurrently with above agents, there can be elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions. Patients may be enrolled on the study if at least 7 days have elapsed since last dose of such a medication.
  • Women who are pregnant or lactating are not eligible. Women of childbearing age musthave a negative pregnancy test within 3 days of treatment and agree to use of contraception during the study period.
  • Use of any of the CYP450 inducers like phenytoin, carbamazepine, barbiturates, rifimapicin, rifabutin or St John's wort within 30 days.

Sites / Locations

  • SUNY Upstate Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Fosparepitant administered in 1st cycle

Fosaprepitant administered in 2nd cycle

Arm Description

Fosaprepitant (Emend) for Injection 150 mg is administered, one time, intravenously on day 1 only, as an infusion with a duration of 30 minutes. It will be initiated approximately 30 minutes prior to the subjects first chemotherapy cycle. An intravenous saline placebo will be administered on day 1 of the second chemotherapy cycle, in the same manor as EMEND for Injection.

Subject will receive a saline Placebo intravenously on day 1 of their first chemotherapy cycle. For the subject's second chemotherapy cycle, EMEND for Injection 150 mg is administered, one time, intravenously on day 1, as an infusion with a duration of 30 minutes. It will be initiated approximately 30 minutes prior to the subjects second chemotherapy cycle.

Outcomes

Primary Outcome Measures

Assess the impact of addition of fosaprepitant upon the complete response (C.R.) rate (no emetic episodes or use of rescue medications) in patients with advanced NSCLC receiving carboplatin-based combination chemotherapy.
The primary end point of the study is to determine the proportion of patients in each of the two groups (placebo and fosaprepitant) who achieve a CR, defined as no vomiting, no retching and no rescue therapy during days 1-5 following the first two cycles of carboplatin based combination chemotherapy using an intent to-treat (ITT) analysis.

Secondary Outcome Measures

No emesis (defined as no emetic episodes regardless of use of rescue therapy)
No emesis (defined as no emetic episodes regardless of use of rescue therapy)
Asses nausea based on visual analog scale (VAS)
Assessment of nausea based on visual analog scale (VAS) and symptoms measured by M. D. Anderson Symptom Inventory to capture the following end points: No nausea (maximum VAS <5 mm on a 0 to 100 mm scale) No significant nausea (maximum VAS <25 mm on a 0 to 100 mm scale) Complete protection (defined as no emetic episodes, no use of rescue therapy, and a maximum nausea visual analogue scale [VAS] score <25 mm on a 0 to 100 mm scale)
Patient's preferred cycle
After the 2 cycles, determine patient's stated preferred cycle.

Full Information

First Posted
March 20, 2015
Last Updated
April 2, 2015
Sponsor
Ajeet Gajra
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02407600
Brief Title
Study Assessing Fosaprepitant in Advanced NSCLC Patients Treated With Carboplatin Based Chemotherapy
Official Title
Phase II, Double-blind, Placebo-controlled, Crossover Study Evaluating a 5HT3 Antagonist Plus Dexamethasone With or Without Fosaprepitant in Patients With Advanced NSCLC Receiving Carboplatin Based Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Unknown status
Study Start Date
April 2015 (undefined)
Primary Completion Date
February 2018 (Anticipated)
Study Completion Date
February 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ajeet Gajra
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study evaluates the addition of fosaprepitant to currently available antiemtic treatments of carboplatin chemotherapy-induced nausea and vomiting in advanced non-small cell lung cancer patients. Half of the patients will receive fosaprepitant in their first chemotherapy cycle, and a placebo on their second chemotherapy cycle. The other half of the patients will begin their first chemotherapy cycle.
Detailed Description
The addition of aprepitant to 5HT-3 antagonist and steroid is approved for the prevention of acute and delayed nausea for highly emetogenic chemotherapy (HEC). The use of oral aprepitant 3 day regimen has been evaluated in moderately emetogenic chemotherapy. However, its use has not been explored in carboplatin containing combination regimens in advanced non-small cell lung cancer (NSCLC). An equivalency study compared fosaprepitant, a 1-day intravenous formulation of aprepitant, with oral aprepitant. Findings demonstrate equivalence between the agents for complete response and both emesis and nausea control. Fosaprepitant was endorsed by the ASCO Update Committee as an acceptable NK1 receptor antagonist. However, there has been no evaluation of this iv formulation with moderately emetogenic chemotherapy and specifically carboplatin containing regimens in NSCLC. Therefore, the investigators propose a double-blind, randomized placebo controlled cross-over phase II study assessing the role of fosaprepitant in the prevention of nausea and emesis in patients receiving carboplatin based chemotherapy for advanced NSCLC. Patients will be treated with Emend/ placebo administered intravenously on day 1 of cycles 1 of carboplatin based chemotherapy with crossover to the alternate agent (placebo/ Emend) on day 1 of cycle 2 with each cycle being 21 days. Fosaprepitant will be administered intravenously on day 1 of either cycle 1 or cycle 2 prior to carboplatin based chemotherapy. Placebo will be administered as the alternative agent. Study team and the subject will be blinded to fosaprepitant versus placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, Vomiting, Nausea, Emesis
Keywords
EMEND for Injection, 5HT-3, Fosaprepitant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fosparepitant administered in 1st cycle
Arm Type
Active Comparator
Arm Description
Fosaprepitant (Emend) for Injection 150 mg is administered, one time, intravenously on day 1 only, as an infusion with a duration of 30 minutes. It will be initiated approximately 30 minutes prior to the subjects first chemotherapy cycle. An intravenous saline placebo will be administered on day 1 of the second chemotherapy cycle, in the same manor as EMEND for Injection.
Arm Title
Fosaprepitant administered in 2nd cycle
Arm Type
Sham Comparator
Arm Description
Subject will receive a saline Placebo intravenously on day 1 of their first chemotherapy cycle. For the subject's second chemotherapy cycle, EMEND for Injection 150 mg is administered, one time, intravenously on day 1, as an infusion with a duration of 30 minutes. It will be initiated approximately 30 minutes prior to the subjects second chemotherapy cycle.
Intervention Type
Drug
Intervention Name(s)
FOSAPREPITANT (Emend)
Other Intervention Name(s)
EMEND for Injection
Intervention Description
Uee of fosprepitant in EITHER first OR 2nd cycle of carboplatin containing combination chemotherapy in patients with advanced NSCLC
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Assess the impact of addition of fosaprepitant upon the complete response (C.R.) rate (no emetic episodes or use of rescue medications) in patients with advanced NSCLC receiving carboplatin-based combination chemotherapy.
Description
The primary end point of the study is to determine the proportion of patients in each of the two groups (placebo and fosaprepitant) who achieve a CR, defined as no vomiting, no retching and no rescue therapy during days 1-5 following the first two cycles of carboplatin based combination chemotherapy using an intent to-treat (ITT) analysis.
Time Frame
Days 1-5 following the first two cycles of carboplatin based combination chemotherapy
Secondary Outcome Measure Information:
Title
No emesis (defined as no emetic episodes regardless of use of rescue therapy)
Description
No emesis (defined as no emetic episodes regardless of use of rescue therapy)
Time Frame
Collection of data at the completion of 2 cycles, day 42.
Title
Asses nausea based on visual analog scale (VAS)
Description
Assessment of nausea based on visual analog scale (VAS) and symptoms measured by M. D. Anderson Symptom Inventory to capture the following end points: No nausea (maximum VAS <5 mm on a 0 to 100 mm scale) No significant nausea (maximum VAS <25 mm on a 0 to 100 mm scale) Complete protection (defined as no emetic episodes, no use of rescue therapy, and a maximum nausea visual analogue scale [VAS] score <25 mm on a 0 to 100 mm scale)
Time Frame
Collection of data at the completion of 2 cycles, day 42.
Title
Patient's preferred cycle
Description
After the 2 cycles, determine patient's stated preferred cycle.
Time Frame
Collection of data at the completion of 2 cycles, day 42.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient age > 18 years and able to sign informed consent. ECOG PS 0-2 Patients with stage IV or recurrent NSCLC being treated with carboplatin based regimen with palliative intent. Acceptable chemotherapy regimens include: Carboplatin (AUC of 5 OR 6) q 21 days with: Paclitaxel Q 21 days OR Docetaxel Q 21 days OR Pemetrexed Q 21 days (non-squamous histology with Vitamin B12 and folate supplementation) OR Gemcitabine administered days 1 and 8 Q 21 days OR Vinorelbine administered days 1 and 8 Q 21 days The addition of bevacizumab to chemotherapy is permitted where indicated and clinically appropriate. Patients who have received prior adjuvant chemotherapy for lung cancer ( > 1 year prior) and have recurred are eligible if it has been > 1 year since completion of adjuvant chemotherapy. Patients who have been treated for locally advanced lung cancer with concurrent chemoradiation but completed such therapy > 1 year ago are eligible provided they meet all other inclusion criteria. Patients who have received prior adjuvant chemotherapy for lung cancer ( > 1 year prior) and have recurred are eligible if it has been > 1 year since completion of adjuvant chemotherapy. Patients who have been treated for locally advanced lung cancer with concurrent chemoradiation but completed such therapy > 1 year ago are eligible provided they meet all other inclusion criteria. Laboratory parameters: Serum creatinine < 2.0 and AST, ALT < 3 time the upper limit of normal Platelet count ≥ 100,00/cumm ANC ≥ 1500/ cumm on day of therapy (day # 1 of the cycle) Hemoglobin > 8.0 g/dl Exclusion Criteria: History of allergic reaction to aprepitant or fosaprepitant Use of other investigational agents concurrently with chemotherapy Uncontrolled systemic hypertension with SBP > 180 and/ or DBP> 110 Concurrent use of pimozide, terfenadine, astemizole, or cisapride (fosaprepitatnt is a dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). If used concurrently with above agents, there can be elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions. Patients may be enrolled on the study if at least 7 days have elapsed since last dose of such a medication. Women who are pregnant or lactating are not eligible. Women of childbearing age musthave a negative pregnancy test within 3 days of treatment and agree to use of contraception during the study period. Use of any of the CYP450 inducers like phenytoin, carbamazepine, barbiturates, rifimapicin, rifabutin or St John's wort within 30 days.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ajeet Gajra, MD FACP
Phone
(315) 464-5934
Email
gajraa@upstate.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kristine M Garcia, BS
Phone
(315) 464-5934
Email
garciakr@upstate.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajeet Gajra, MD FACP
Organizational Affiliation
State University of New York - Upstate Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristine Garcia, BS
Phone
315-464-5934
First Name & Middle Initial & Last Name & Degree
Dena Martin, BS
Phone
3154645262
First Name & Middle Initial & Last Name & Degree
Ajeet Gajra, MD FACP

12. IPD Sharing Statement

Citations:
PubMed Identifier
22460057
Citation
Fernandez-Ortega P, Caloto MT, Chirveches E, Marquilles R, Francisco JS, Quesada A, Suarez C, Zorrilla I, Gomez J, Zabaleta P, Nocea G, Llombart-Cussac A. Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients' quality of life. Support Care Cancer. 2012 Dec;20(12):3141-8. doi: 10.1007/s00520-012-1448-1. Epub 2012 Mar 31.
Results Reference
background
PubMed Identifier
20354457
Citation
Wheatley-Price P, Le Maitre A, Ding K, Leighl N, Hirsh V, Seymour L, Bezjak A, Shepherd FA; NCIC Clinical Trials Group. The influence of sex on efficacy, adverse events, quality of life, and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group non-small cell lung cancer chemotherapy trials. J Thorac Oncol. 2010 May;5(5):640-8. doi: 10.1097/JTO.0b013e3181d40a1b.
Results Reference
background
PubMed Identifier
8996130
Citation
Hesketh PJ, Kris MG, Grunberg SM, Beck T, Hainsworth JD, Harker G, Aapro MS, Gandara D, Lindley CM. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol. 1997 Jan;15(1):103-9. doi: 10.1200/JCO.1997.15.1.103.
Results Reference
background
PubMed Identifier
20972805
Citation
Grunberg SM, Warr D, Gralla RJ, Rapoport BL, Hesketh PJ, Jordan K, Espersen BT. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--state of the art. Support Care Cancer. 2011 Mar;19 Suppl 1:S43-7. doi: 10.1007/s00520-010-1003-x. Epub 2010 Oct 24.
Results Reference
background

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Study Assessing Fosaprepitant in Advanced NSCLC Patients Treated With Carboplatin Based Chemotherapy

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