A Trial of Amrubicin and Carboplatin With Pegfilgrastim in Patients With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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This proposed trial will investigate the combination of amrubicin and carboplatin in the first-line treatment of patients with extensive-stage small cell lung cancer (ES- SCLC). Since myelosuppression is the most common toxicity produced by this drug combination, pegfilgrastim will be administered with each treatment cycle. This trial will be the first clinical trial to evaluate a combination of amrubicin and carboplatin in the first-line treatment of ES SCLC in a U.S. population.

Official Title
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A Phase II Trial of Amrubicin and Carboplatin With Pegfilgrastim in Patients With Extensive-Stage Small Cell Lung Cancer

Conditions
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Extensive-Stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Amrubicin
* Drug: Carboplatin
* Drug: Pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically and/or histologically confirmed small-cell lung cancer with extensive stage disease. Measurable or evaluable disease per RECIST criteria version 1.1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1. Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA). QTc interval of ≤450 msec. on ECG. Adequate organ function, including the following: ANC ≥1500 cells/micro liter Platelet count ≥100,000 cells/micro liter Hemoglobin ≥9 g/dL Total bilirubin ≤1.5 x ULN; AST/ALT ≤2.5 x ULN, (except if due to hepatic metastases, then ≤5 x ULN) Serum creatinine ≤1.5 x ULN Patients must be able to receive growth factors (G-CSF). Women of childbearing potential must have a negative serum or urine pregnancy test performed ≤ 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Patients ≥18 years of age. Patients must be accessible for treatment and follow-up. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry. Exclusion Criteria: Previous treatment for limited-stage SCLC. Previous chemotherapy or radiation therapy for SCLC (unless radiation was administered for brain metastases). Active brain metastases. Patients with treated brain metastases are eligible, if (1) radiation therapy was completed ≥ 21 days prior to first dose of amrubicin; (2) follow-up scan shows no disease progression; an absence of neurologic symptoms and (3) patient does not require steroids. Mixed small cell/non-small cell tumors or other neuroendocrine lung cancers. Women who are pregnant or breastfeeding. Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis. Patients with New York Heart Association (NYHA) class II or greater congestive heart failure (CHF). Any of the following ≤6 months prior to starting study treatment: myocardial infarction; severe unstable angina; ongoing cardiac dysrhythmia. Family history of idiopathic cardiomyopathy or uncontrolled heart arrhythmia. Treatment for other invasive cancers during the previous 5 years, or the presence of any active invasive cancer of any type (with the exception of non-melanoma skin cancers). Uncontrolled hypertension (i.e., blood pressure >150/90 mmHg that cannot be controlled with standard anti-hypertensive agents). Major surgical procedure or significant traumatic injury ≤ 28 days of study initiation. History of seropositive HIV or patients who are receiving immunosuppressive medications that would in the opinion of the investigator increase the risk of the serious neutropenic complications. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study. Use of any non-approved or investigational agent ≤30 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amrubicin/Carboplatin with Pegfilgrastim<br>Systemic therapy | Drug: Amrubicin<br>* 30 mg/m2 IV on Days 1-3 of each 3-week treatment cycle<br>* Other names: SM-5887;Drug: Carboplatin<br>* AUC=5 IV, Day 1 of each 3-week treatment cycle<br>* Other names: Paraplatin-AQ;Drug: Pegfilgrastim<br>* 6 mg SQ on Day 4 of each 3 week treatment cycle<br>* Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year Survival | Percentage of patients still alive one year after their first treatment | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. | 36 months | 
| Time to Progression | Time to progression will be defined as the time from first treatment until objective tumor progression (PD). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 36 months | 
| Overall Survival | The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 84 months | 
| Toxicity/Safety | Grade 3/4 toxicities | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCLC, Amrubicin, Carboplatin, Pegfilgrastim, Neulasta