Single Agent Versus Combination Chemotherapy to Treat High-risk Elderly With Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This study will enroll elderly patients with advanced non-small cell lung cancer who are at high risk of developing chemotherapy toxicity (side effects). Patients will receive treatment with either a platinum-based doublet chemotherapy with carboplatin/nab-paclitaxel or single agent nab-paclitaxel of chemotherapy. Response to treatment and treatment toxicity will be compared in the two treatment groups to determine the best treatment strategy for this group of patients.

Detailed Description
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The primary objective of this trial is to compare the treatment failure-free survival rate in high-risk elderly patients, identified by geriatric assessment, treated with either a platinum-based doublet chemotherapy with carboplatin/nab-paclitaxel or single agent nab-paclitaxel in advanced non-small cell lung cancer. Treatment failure-free survival is the most appropriate primary outcome as it captures excessive toxicity due to chemotherapy in addition to death and disease progression. The secondary objectives are to evaluate grade 3-5 toxicities, overall response rate, progression free survival, symptom assessment, and overall survival between the two randomization arms.

Official Title
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A Randomized Phase II Trial of Combination Versus Single Agent Chemotherapy in High-risk Elderly Patients With Advanced Non-small Cell Lung Cancer

Conditions
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Carcinoma, Non-small Cell Lung

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient able and willing to comply with study procedures as per protocol, including the geriatric assessment at the time of study enrollment. Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures. Patients must have histological or cytological confirmed primary non-small cell lung cancer (adenocarcinoma, large cell carcinoma, squamous, or unspecified). Disease must be stage IV Non-Small Cell Lung Cancer (NSCLC). Disease may be either newly diagnosed or recurrent after previous surgery and/or irradiation. Primary or metastatic site for biopsy is allowed Patients may have measurable or non-measurable disease documented by CT or MRI. The CT from a combined PET/CT may be used to document only non-measurable disease. Measurable disease must be assessed within 30 days prior to registration per response evaluation criteria in solid tumors (RECIST) v1.1. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non- measurable disease must be assessed within 30 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Prior chemotherapy for curative intent is permitted providing the cytotoxic chemotherapy was completed ≥12 months prior to enrollment. Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 30 days prior to registration. Patient must not have brain metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least 1 day. Any radiation therapy completed prior to chemotherapy, except gamma-knife radiosurgery, 1 week prior to chemotherapy. Age >70 years of age at time of signing of the informed consent form. Life expectancy of greater than 12 weeks. ECOG performance status 0-2 (See Appendix A) Patients must have a comprehensive geriatric assessment and chemotherapy toxicity assessment score between 7-17 (See Appendix B, D) Patients must have normal organ and marrow function as defined below: Leukocytes >3,000/mcL ANC > 1,500 cells/mm3Hemoglobin > 9.0g/dL Platelets >100,000 cells/mm3 Total bilirubin < 1.5 mg/dL (unless there is a known history of Gilberts Syndrome). AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal Alkaline phosphatase < 2.5 X upper limit of normal in the absence of liver or bone metastasis, or ≤ 5.0 × upper limit of normal range if bone or liver metastases Creatinine clearance >25 mL/min or creatinine <1.5 mg/dL HIV-positive patients on combination antiretroviral therapy are eligible if they have been on ARVs for ≥6 months and undetectable viral loads. Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection. No other priormalignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years. Ability to understand and the willingness to sign a written informed consent document in English or a Spanish consent short form. If language other than English or Spanish, then interpreter will be used to sign English consent form. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE) Exclusion Criteria Patients who have had palliative chemotherapy prior to entering the study <12 months from enrollment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not be receiving any other investigational agents or have received immunotherapy. Known EGFR or ALK mutated disease (molecular testing not required prior to study entry) History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, or nab-paclitaxel. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events v4.0) Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for ≥ 2 weeks prior to signing Informed consent form. Magnetic Resonance Imaging of the brain (or Computed Tomography scan w/contrast) is preferred for diagnosis.

Ages Eligible for Study
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Minimum Age: 71 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Platinum-based doublet chemotherapy<br>Carboplatin AUC 5 30 minute infusion IV on day 1 Nab-paclitaxel 100mg/mg2 30 minute infusion IV on days 1, 8 of a 21 day cycle | Drug: Carboplatin<br> <br> Drug: Nab-paclitaxel<br> <br> |
| Active Comparator: Single agent chemotherapy<br>-Nab-paclitaxel 100mg/mg2 30 minute infusion IV on days 1, 8 of a 21 day cycle | Drug: Nab-paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Failure-free Survival |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | start of treatment to disease progression/recurrence, up to 12 months | 
| Progression-free Survival |  | start of treatment to disease progression, up to 12 months | 
| Overall Survival |  | Up to 12 months | 
| Grade 3-5 Adverse Events | Adverse events were characterized using Common Terminology Criteria for Adverse Events (CTCAE) | Up to week 13 | 
| Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained. | baseline | 
| Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | The higher the score, the greater the symptoms. The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained. Symptoms were measured following 2 21-day cycles of chemotherapy. | week 6 | 
| Symptom Assessment (Measured by FACT-L Symptom Assessment Scale) | The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. Symptoms were measured following 4 21-day cycles of chemotherapy. | week 12 |