A Phase 2 Study of Nab-sirolimus (ABI-009) in Patients With Advanced Malignant PEComa
Condition: Malignant PEComa
MeSH terms: Perivascular Epithelioid Cell Neoplasms
Intervention: nab-Sirolimus
Intervention description: Patients received nab-sirolimus at 100 mg/m2 on Days 1 and 8 of a 21-day cycle by intravenous infusion over 30 minutes.
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: malignant PEComa, perivascular epithelioid cell tumors

Summary:

      A phase 2 multi-center investigation of efficacy of nab-sirolimus (formerly known as ABI-009
      or nab-rapamycin) in patients with advanced malignant perivascular epithelioid cell tumor
      (PEComa).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have a histologically confirmed diagnosis of malignant PEComa that is
             either metastatic or locally advanced and for which surgery is not a recommended
             option.

          2. Patients must have available tumor block along with the corresponding pathology report
             (or approximately 30 unstained slides, with a minimum of 16 slides), and/or fresh
             biopsy to allow retrospective centralized confirmation of malignant PEComa and for
             mTOR pathway analysis and biomarker analysis.

          3. Patients must have one or more measurable target lesions by CT scan or MRI. Measurable
             disease by RECIST v1.1.

          4. Patients must not have been previously treated with an mTOR inhibitor.

          5. Prior treatment (investigational or other), chemotherapy, radiotherapy, surgery, or
             other therapeutic agents (except mTOR inhibitors) is allowed, if completed after 5
             half-lives or ≥28 days prior to enrollment, whichever is shorter.

          6. Eligible patients, 18 years or older, with Eastern Cooperative Oncology Group (ECOG)
             performance status 0 or 1.

          7. Patients must have the following blood chemistry levels at screening (obtained

             ≤14 days prior to enrollment (local laboratory):

               1. total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dl

               2. AST ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases)

               3. serum creatinine ≤1.5 x ULN

          8. Adequate biological parameters as demonstrated by the following blood counts at
             screening (obtained ≤14 days prior to enrollment, local laboratory):

               1. Absolute neutrophil count (ANC) ≥1.5 × 109/L;

               2. Platelet count ≥100,000/mm3 (100 × 109/L);

               3. Hemoglobin ≥9 g/dL.

          9. Serum triglyceride <300 mg/dL; 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 IP and while on study
                  medication 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.

               -  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, 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:

        A patient will not be eligible for inclusion in this study if any of the following criteria
        apply:

          1. Patients with lymphangioleiomyomatosis (LAM) are excluded.

          2. 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.

          3. Active gastrointestinal bleeding, if transfusion dependent.

          4. Pre-existing thyroid abnormality is allowed provided thyroid function can be
             controlled with medication.

          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 pT2 with Gleason Score ≤ 6 and
             postoperative 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. Liver-directed therapy within 2 months of enrollment. Prior treatment with
             radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial
             embolization (with or without chemotherapy) or cyrotherapy/ablation) is allowed if
             these therapies did not affect the areas of measurable disease being used for this
             protocol.

          7. 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).

          8. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.

          9. Unstable coronary artery disease or myocardial infarction during preceding 6 months.

         10. Receiving any concomitant antitumor therapy.

         11. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary
             hypertension.

         12. The use of certain medications and illicit drugs within 5 half-lives or 28 days,
             whichever is shorter prior to the first dose of study drug and for the duration of the
             study will not be allowed.

         13. 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.