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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Nausea, Non-small Cell Lung Cancer, Vomiting, Emesis

Intervention / Treatment
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* Drug: FOSAPREPITANT (Emend)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fosparepitant administered in 1st cycle<br>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. | Drug: FOSAPREPITANT (Emend)<br>* Uee of fosprepitant in EITHER first OR 2nd cycle of carboplatin containing combination chemotherapy in patients with advanced NSCLC<br>* Other names: EMEND for Injection;Drug: Placebo<br> <br> |
| Sham Comparator: Fosaprepitant administered in 2nd cycle<br>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. | Drug: FOSAPREPITANT (Emend)<br>* Uee of fosprepitant in EITHER first OR 2nd cycle of carboplatin containing combination chemotherapy in patients with advanced NSCLC<br>* Other names: EMEND for Injection;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 1-5 following the first two cycles of carboplatin based combination chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Collection of data at the completion of 2 cycles, day 42. | 
| 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) | Collection of data at the completion of 2 cycles, day 42. | 
| Patient's preferred cycle | After the 2 cycles, determine patient's stated preferred cycle. | Collection of data at the completion of 2 cycles, day 42. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EMEND for Injection, 5HT-3, Fosaprepitant