BrUOG L301 With Non-Small Cell Lung Cancer and Bone Metastases

Study Overview
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Brief Summary
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In this study patient's will receive the medicine Xofigo which is a radioactive drug that is FDA approved to treat prostate cancer that has spread to the bones. Xofigo has not previously been tested to treat lung cancer that has spread to the bones. Your doctors are studying the effects, good and bad, of Xofigo when used to treat lung cancer that has spread to the bones.

Detailed Description
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In this study patient's will receive the medicine Xofigo which is a radioactive drug that is FDA approved to treat prostate cancer that has spread to the bones. Xofigo has not previously been tested to treat lung cancer that has spread to the bones. Your doctors are studying the effects, good and bad, of Xofigo when used to treat lung cancer that has spread to the bones. Your doctors will also be evaluating changes in health related quality of life using the EORC QL-C20 and QOL-BM22 questionnaires. They will also evaluate the impact of treatment on the Alkaline phosphate levels (by way of lab draws) in patients and measure the progression free survival and overall survival of patients with stable or responding disease after the front line chemotherapy treated with Xofigo.

Official Title
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BrUOG L301: Xofigo Following Frontline-Line Chemotherapy For Patients With Non-Small Cell Lung Cancer and Bone Metastases

Conditions
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Non Small Cell Lung Cancer With Bone Metastatses

Intervention / Treatment
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* Biological: Xofigo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Advanced non-small cell lung cancer with bone metastases. Stable or responding disease after completion of initial systemic chemotherapy as defined by RECIST criteria. Site to submit confirmation to BrUOG. At least 3 weeks must have elapsed since completion of last chemotherapy and 4 weeks since last radiation, prior to first dose of Xofigo. Patients are not permitted to receive any form of 'maintenance' chemotherapy or biologic/targeted anticancer therapy while being treated on this study Life expectancy of at least 12 weeks (3 months). Patients with treated brain metastases are allowed, but must have brain imaging showing evidence of stability since most recent treatment for brain mets, prior to first dose of Xofigo. For patients with brain metastases only, brain imaging is required. Patients who do not have brain metastases or symptoms of potential brain metastases are not required to have baseline brain imaging, but this must be confirmed in writing Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1. Required entry laboratory parameters within 14 days of study entry: White Blood Cell Count (WBC) ≥ 3,000/mm3; Absolute Neutrophil Count (ANC) ≥ 1,500/mm3; Platelet (PLT) count ≥ 100,000/mm3; Hemoglobin (Hgb) > 9g/dl, Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN ; Creatinine ≤ 1.5 x ULN; Albumin > 2.5 g/dL. Concurrent treatment with bisphosphonates and denosumab is allowed. Information on start and stop date and drug with dose to be sent to BrUOG if patient to be treated concurrently. Prior skeletal related events (pathologic fracture, radiation or surgery to bone, or spinal cord compression) are allowed if they have been managed and now patient is stable for 4 weeks prior to study entry. Must submit how events managed to BrUOG for documentation to confirm eligibility criterion. (For example, if a patient experienced a SSE and had radiation for 2 weeks they must then be stable for 4 weeks after the completion of radiation prior to study entry) Subjects must be able to understand and be willing to sign the written informed consent form. All acute toxic effects related to prior treatment(s) must have resolved to NCI-CTCAE v4 Grade 1 or less at the time of signing the Informed Consent Form (ICF) except for alopecia. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the treating physician. Willing and able to comply with the protocol, including follow-up visits and examinations Exclusion Criteria: Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases No prior invasive malignancy within the prior two years. However, patients with an early stage malignancy that is not expected to require treatment in the next 2 years (such as early stage, resected breast cancer or asymptomatic prostate cancer) are eligible Untreated brain metastases. Any other serious illness or medical condition that in the investigator's opinion would interfere with protocol treatment, such as but not limited to: Any active infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 Grade 2: Cardiac failure New York Heart Association (NYHA) III or IV Women who are pregnant or breast-feeding. Inability to comply with the protocol and/or not willing or who will not be available for follow-up assessments. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation. Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than Ra 223 dichloride. Major surgery within 28 days of starting study drug. Central venous catheter placement is not considered major surgery.

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: Xofigo<br>Xofigo, 50 kBq/kg body weight, will be administered in the nuclear medicine department as a bolus intravenous (IV) injection (up to 1 minute) at intervals of every 4 weeks for up to 6 cycles. | Biological: Xofigo<br>* This is a radio-isotope<br>* Other names: Radium -223;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Symptomatic Skeletal Events (SSE) in Patients Receiving Xofigo With NSCLC and Bone Metastases | Number of Participants with Symptomatic Skeletal Events (SSE) Receiving Xofigo With NSCLC and Bone Metastases | Approximately every 2 months for up to a year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival of Patients With NSCLC and Bone Metastases and Stable or Responding Disease After Front-line Chemotherapy Treated With Xofigo | To measure progression-free survival of patients with NSCLC and bone metastases and stable or responding disease after front-line chemotherapy treated with Xofigo. Post 1 year of follow up the number of patients that remain stable or responding | During treatment (6 cycles, 1 cycle=4 weeks) and through 1 year post treatment | 
| Overall Survival of Patients With NSCLC and Bone Metastases and Stable or Responding Disease After Front-line Chemotherapy Treated With Xofigo | To measure overall survival of patients with NSCLC and bone metastases and stable or responding disease after front-line chemotherapy treated with Xofigo | During treatment (6 cycles, 1 cycle=4 weeks) and through 1 year post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NCSLC, lung cancer, non small cell lung cancer, bone metastases, maintenance