A Study to testABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System
Condition: Neuroendocrine Tumors
MeSH terms: Neuroendocrine Tumors; Lung Neoplasms
Intervention: ABI-009
Intervention description: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Unresectable or metastatic patients with typical or atypical carcinoid tumors of the
             lung or low or intermediate grade gastroenteropancreatic neuroendocrine tumors
             (GEPNETs).

          2. Patients must have measurable disease per RECIST 1.1.

          3. Patients must have progressed on everolimus or been intolerant to everolimus.

          4. Patients, ≥18 years old, must have Eastern Cooperative Oncology Group (ECOG)
             Performance Status 0 or 1.

          5. Concurrent use of somatostatin analogs (SSAs) is allowed if currently used for symptom
             control.

          6. Adequate liver function:

               1. Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL

               2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN
                  (<5 x ULN if the patient has liver metastases).

          7. Adequate renal function:

             a. Serum creatinine ≤2 x ULN or creatinine clearance >50 cc/hr (Cockroft-Gault).

          8. Adequate biological parameters:

               1. Absolute neutrophil count (ANC) ≥1.5 × 109/L

               2. Platelet count ≥100,000/mm3 (100 × 109/L)

               3. Hemoglobin ≥9 g/dL.

          9. Fasting serum triglyceride ≤300 mg/dL; fasting serum cholesterol ≤350 mg/dL.

         10. 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.

         11. Life expectancy of >3 months, as determined by the investigator.

         12. Ability to understand and sign informed consent.

         13. Willingness and ability to comply with scheduled visits, laboratory tests, and other
             study procedures.

        Exclusion Criteria:

          1. Patients currently undergoing anti-cancer therapy for neuroendocrine tumors (other
             than SSAs for symptoms).

          2. History of allergic reactions to compounds of similar chemical or biologic composition
             to ABI-009.

          3. 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.

          4. Active gastrointestinal bleeding.

          5. 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).

          6. 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).

          7. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.

          8. Unstable coronary artery disease or myocardial infarction during preceding 6 months.

          9. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary
             hypertension.

         10. 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.

         11. Known Human Immunodeficiency Virus (HIV).

         12. Known active Hepatitis B or Hepatitis C.