Single Arm on the Tolerability of Weekly Nab-paclitaxel

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of weekly nab-paclitaxel for a second-line treatment in elderly subjects, 70 years of age or greater, with non-small cell lung cancer (NSCLC)

Detailed Description
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This will be a non-randomized phase II study evaluating the safety and efficacy of weekly nab-paclitaxel for second-line treatment in 42 elderly patients, who are 70 years of age or greater with non-small cell lung cancer (NSLC). Patients will be required to have progressed on a single prior regimen. Nab-paclitaxel 100mg/m2 will be administered intravenously, weekly for 3 weeks of every 4-week cycle. After every two cycles of therapy, imaging will be performed to assess for response. Patients will be eligible to continue receiving therapy until the time of disease progression. Primary Objectives To evaluate the tolerability of weekly nab-paclitaxel in older adults with advanced lung cancer who have progressed on at least 1 prior regimen after 6 cycles or 3 weeks after discontinuation of treatment, for those who come off treatment earlier. Secondary Objectives To estimate overall survival To estimate progression-free survival To estimate the response rate Correlative Objectives To explore baseline components of the Geriatric Assessment (GA) as predictors of chemotherapy tolerance and overall survival To explore the use of p16 measurements in the elderly as predictors of chemotherapy tolerance and overall survival To explore the impact of weekly nab-paclitaxel treatment on quality of life, as measured by Lung Cancer Symptom Scale (LCSS) and Functional Assessment of Cancer Therapy-Lung (FACT-L).

Official Title
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LCCC 1210 - Phase II, Multicenter, Single Arm Study of the Tolerability of Weekly Nab-paclitaxel as Second Line Treatment for Elderly Patients With Advanced Lung Cancer

Conditions
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Non Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Nab-Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Male or female patient Greater than or equal to 70 years of age Diagnosis of NSCLC histologically or cytologically confirmed Internal Association for the Study of Lung Cancer Version 7 Stage IV disease or recurrence after prior surgery or radiotherapy Progression following one line of prior chemotherapy consisting of a platinum agent plus a standard cytotoxic partner agent other than a taxane, typically pemetrexed gemcitabine or vinorelbine A single agent non cytoxic regimen if the patient has a molecular change that the non cytotoxic regimen would be expected to be efficacious for epidermal growth factor receptor (EGFR) mutation for erlotinib and (EML4) anaplastic lymphoma kinase (ALk) or ROS1 for crizotinib Eastern Cooperative Oncology Group performance status 0 to 2 Adequate organ and bone marrow function as defined by Absolute neutrophil count greater than or equal to 1500 cells/mm3 Creatinine less than or equal to 1.5 mg dL Total bilirubin less than or equal to 1.5 mg dL Alkaline phosphatase less than or equal to 2.5 x upper limit of normal Alanine aminotransferase less than or equal to 2.5 x upper limit of normal Aspartate aminotransferase less than or equal to 2.5 upper limit of normal Recovered from all reversible toxicities related to their previous treatment to less than or equal to grade 1 or baseline Patients must have equal to grade 2 pre existing peripheral neuropathy Women of childbearing potential and sexually active men must agree to use effective contraception prior to study entry for the duration of study participation and for three months after completing treatment. Adequate contraception is defined as any medically recommended method as per standard of care Negative serum or urine bhCG pregnancy test at screening for patients of childbearing potential Patients with brain metastases may participate if they have undergone appropriate treatment for the lesions are at least two weeks post treatment without evidence for post treatment progression have no significant neurologic symptoms and no longer require steroids for the reason of brain metastases. Patients with symptoms suggestive of central nervous system (CNS) metastases should be evaluated with imaging prior to study participation Exclusion Criteria: Prior taxane therapy for any indication Less than 3 weeks elapsed since prior exposure to chemotherapy Pre existing neuropathy greater than grade 1 Other active invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years localized squamous cell carcinoma of the skin basal cell carcinoma of the skin, carcinoma in situ of teh cervix or other malignancies requiring locally ablative therapy only will not result in exclusion Concomitant anticancer therapy immunotherapy or radiation therapy within prior 4 weeks Have received treatment within the last 30 days prior to study entry with any drug that has not receive regulatory approval for an indication at the time of study entry Uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring IV antibiotics symptomatic congestive heart failure unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of nab paclitaxel because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study Known hypersensitivity to protein bound paclitaxel Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol

Ages Eligible for Study
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Minimum Age: 70 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: nab paclitaxel<br>Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle | Drug: Nab-Paclitaxel<br>* Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Without Any Adverse Events Grade 3 or Higher | Tolerability of weekly nab-paclitaxel, as measured by occurrence of Grade 3 or worse toxicity after 6 cycles or 3 weeks after discontinuation of treatment, for those who came off treatment earlier as measured by the NCI Common Terminology Criteria for Adverse Events CTCAE, version 4. The CTCAE is a descriptive terminology utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | 168 days after start of treatment (6 cycles) (or 3 weeks after discontinuation of treatment, for those who come off treatment earlier) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival | Overall Survival is defined as the time from day 1 (D1) of treatment until death as a result of any cause | up to 2 years after end of treatment (treatment lasts up to 168 days (up to 6 cycles of 28 days each)) | 
| Median Progression Free Survival | Progression free survival is defined as the time from D1 of treatment until progression or death as a result of any cause. Progressive Disease (PD) is determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. PD is at least a 20% increase in the sum of the longest diameters (LD) of the target lesions taking as reference the smallest sum LD recorded since the treatment started including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of one or more new lesions also constitutes PD. | up to 2 years after end of treatment (treatment lasts up to 168 days (up to 6 cycles of 28 days each)) | 
| Overall Response Rate | Response will be measured by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. The Overall Response rate is defined as the percentage of participants with CR or PR | 168 days after start of treatment (6 cycles) (or 3 weeks after discontinuation of treatment, for those who come off treatment earlier) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UNC, Nab paclitaxel, Abraxane, First Line, Non small cell lung cancer, NSCLC, Phase II, Non-Randomized, Elderly, Lineberger, LCCC 1210