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

NCT ID: NCT02407600

Last Updated: 2015-04-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2018-02-28

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.

Conditions

Non-small Cell Lung Cancer; Vomiting; Nausea; Emesis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fosparepitant administered in 1st cycle

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.

Group Type: ACTIVE_COMPARATOR

FOSAPREPITANT (Emend)

Intervention Type: DRUG

Uee of fosprepitant in EITHER first OR 2nd cycle of carboplatin containing combination chemotherapy in patients with advanced NSCLC

Placebo

Intervention Type: DRUG

Fosaprepitant administered in 2nd cycle

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.

Group Type: SHAM_COMPARATOR

FOSAPREPITANT (Emend)

Intervention Type: DRUG

Uee of fosprepitant in EITHER first OR 2nd cycle of carboplatin containing combination chemotherapy in patients with advanced NSCLC

Placebo

Intervention Type: DRUG

Interventions

FOSAPREPITANT (Emend)

Uee of fosprepitant in EITHER first OR 2nd cycle of carboplatin containing combination chemotherapy in patients with advanced NSCLC

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

EMEND for Injection

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 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Ajeet Gajra

OTHER

Sponsor Role: lead

Responsible Party

Ajeet Gajra

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ajeet Gajra, MD FACP

Role: PRINCIPAL_INVESTIGATOR

State University of New York - Upstate Medical University

Locations

SUNY Upstate Medical University

Syracuse, New York, United States

Countries

United States

Central Contacts

Ajeet Gajra, MD FACP

Role: CONTACT

gajraa@upstate.edu

(315) 464-5934

Kristine M Garcia, BS

Role: CONTACT

garciakr@upstate.edu

(315) 464-5934

Facility Contacts

Kristine Garcia, BS

Role: primary

315-464-5934

Dena Martin, BS

Role: backup

3154645262

References

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.

Reference Type: BACKGROUND

PMID: 22460057 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20354457 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8996130 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20972805 (View on PubMed)

Other Identifiers

Merck-50437

Identifier Type: -

Identifier Source: org_study_id