Clinical trial NCT02407600: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Vomiting
Nausea
Emesis
Keywords: EMEND for Injection
5HT-3
Fosaprepitant
Lead sponsor: State University of New York - Upstate Medical University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-04-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: Days 1-5 following the first two cycles of carboplatin based combination chemotherapy
Secondary outcomes:
measure: No emesis (defined as no emetic episodes regardless of use of rescue therapy)
timeFrame: Collection of data at the completion of 2 cycles, day 42.
measure: Asses nausea based on visual analog scale (VAS)
timeFrame: Collection of data at the completion of 2 cycles, day 42.
measure: Patient's preferred cycle
timeFrame: Collection of data at the completion of 2 cycles, day 42.
Other outcomes:
Locations:
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
Study officials:
affiliation: State University of New York - Upstate Medical University
name: Ajeet Gajra, MD FACP
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.