A Study to testABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ABI-009 will make advanced, malignant neuroendocrine tumor(s) of the lung, gastrointestinal tract and/or pancreas that cannot be removed by surgery smaller and slow the spread of your cancer in patients who have progressed or been intolerant to everolimus. All eligible participants will receive ABI-009, the study drug.

Detailed Description
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ABI-009, human albumin-bound rapamycin, is an experimental drug. Experimental means that the drug has not been approved by the Food and Drug Administration (FDA). Rapamycin, the active part of the drug, inhibits a biological pathway (mTOR) that certain cancers use to grow. Rapamycin and similar types of drugs have been used in many other tumors, including advanced renal cell carcinoma. A standard mTOR inhibitor used in neuroendocrine tumors is everolimus. The human albumin component of ABI-009 may allow rapamycin to reach cancer cells more effectively. ABI-009 has not been approved for the treatment of advanced, malignant neuroendocrine tumors of the lung, gastrointestinal tract and/or pancreas. The information from this study might help us identify if ABI-009 is safe and effective in this disease.

Official Title
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A Pilot Phase 2 Study of Albumin-bound Rapamycin Nanoparticles, ABI-009, in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: ABI-009


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable or metastatic patients with typical or atypical carcinoid tumors of the lung or low or intermediate grade gastroenteropancreatic neuroendocrine tumors (GEPNETs). Patients must have measurable disease per RECIST 1.1. Patients must have progressed on everolimus or been intolerant to everolimus. Patients, ≥18 years old, must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Concurrent use of somatostatin analogs (SSAs) is allowed if currently used for symptom control. Adequate liver function: Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (<5 x ULN if the patient has liver metastases). Adequate renal function: a. Serum creatinine ≤2 x ULN or creatinine clearance >50 cc/hr (Cockroft-Gault). Adequate biological parameters: Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelet count ≥100,000/mm3 (100 × 109/L) Hemoglobin ≥9 g/dL. Fasting serum triglyceride ≤300 mg/dL; fasting serum cholesterol ≤350 mg/dL. Male or non-pregnant and non-breast feeding female: Females of child-bearing potential must agree to use effective contraception without interruption from 28 days prior to starting investigational product (IP) throughout 3 months after last dose of IP and have a negative serum pregnancy test (β-hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation. Male patients must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study and throughout 3 months after last dose of IP. A second form of birth control is required even if he has undergone a successful vasectomy. Life expectancy of >3 months, as determined by the investigator. Ability to understand and sign informed consent. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures. Exclusion Criteria: Patients currently undergoing anti-cancer therapy for neuroendocrine tumors (other than SSAs for symptoms). History of allergic reactions to compounds of similar chemical or biologic composition to ABI-009. Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A patient with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases ?28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases. Active gastrointestinal bleeding. Uncontrolled serious medical or psychiatric illness. Patients with a currently active second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pathological tumor-2 (pT2) with Gleason Score ≤6 and postoperative prostate-specific antigen (PSA) <0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. Patients are not considered to have a currently active malignancy if they have completed therapy and are free of disease for ≥1 year). Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection). Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Unstable coronary artery disease or myocardial infarction during preceding 6 months. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving the first dose of ABI-009. Known Human Immunodeficiency Virus (HIV). Known active Hepatitis B or Hepatitis C.

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: ABI-009<br>In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle. | Drug: ABI-009<br>* rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)<br>* Other names: nab-rapamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate at 6 Months Per RECIST v1.1. | Disease control rate at 6 months is the proportion of patients who have partial or complete response or stable disease at 6 months. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects Experiencing Adverse Events | Percent of subjects with >=5% adverse events or grades 3 or 4 adverse events | Continuous from the signing of the informed consent to 28 days after last study treatment, on average 6 months |