Clinical Trials /

Nanoparticle Albumin-Bound Rapamycin and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas

NCT03660930

Description:

This phase I/II trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nanoparticle albumin-bound rapamycin and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nanoparticle Albumin-Bound Rapamycin and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas
  • Official Title: A Phase 1/2 Study of ABI-009 (Nab-Rapamycin) With Pazopanib (VOTRIENT®) in Patients With Advanced Nonadipocytic Soft-Tissue Sarcomas

Clinical Trial IDs

  • ORG STUDY ID: RG1718053
  • SECONDARY ID: 10015
  • SECONDARY ID: NCI-2018-01624
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03660930

Conditions

  • Advanced Soft Tissue Sarcoma
  • Locally Advanced Soft Tissue Sarcoma
  • Metastatic Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
Nanoparticle Albumin-Bound RapamycinNab-Rapamycin, ABI-009Treatment (ABI-009, pazopanib)
Pazopanib hydrochlorideVotrientTreatment (ABI-009, pazopanib)

Purpose

This phase I/II trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nanoparticle albumin-bound rapamycin and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      OUTLINE: This is a phase I, dose-escalation study of nanoparticle albumin-bound rapamycin
      followed by a phase II study.

      Participants receive ABI-009 intravenously (IV) on days 1 and 8 and pazopanib hydrochloride
      orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical
      disease progression, unacceptable toxicity, or until in the opinion of the investigator the
      patient is no longer benefiting from therapy, or at the patient's discretion.

      After completion of study treatment, participants are followed up at 30 days, then every 12
      weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ABI-009, pazopanib)ExperimentalParticipants receive nanoparticle albumin-bound rapamycin IV on days 1 and 8 and pazopanib hydrochloride PO daily on days 1-21. Courses repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.
  • Nanoparticle Albumin-Bound Rapamycin
  • Pazopanib hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of non-adipocytic STS that is
             either metastatic or locally advanced and for which curative therapy is not available,
             surgery is not a recommended option, and pazopanib treatment is indicated.

          -  Subjects must have one or more measurable target lesions by Response Evaluation
             Criteria in Solid Tumors (RECIST) version (v)1.1, assessed via computed tomography
             (CT) scan or magnetic resonance imaging (MRI).

          -  Clinical or radiological progression or failure due to toxicity on at least 1 prior
             regimen of systemic treatment for advanced disease. Subjects may not have received
             more than 4 prior lines of systemic therapy (no more than 2 prior therapies may be
             combination cytotoxic therapies). Neo-adjuvant/adjuvant/maintenance treatments are not
             included for this criterion.

          -  Last dose of prior therapy must have been completed a minimum of 14 days prior to
             start of protocol therapy. All ongoing toxicities related to prior therapy must be
             resolved or grade 1 (except alopecia).

             * NOTE: Toxicities from prior therapy that have resolved with sequalae (e.g.
             hypothyroidism) and are asymptomatic or well-controlled are not exclusionary.

          -  Total bilirubin =< upper limit of normal (ULN) mg/dL (Subjects with known Gilbert's
             syndrome and a total bilirubin =< 3 mg/dl are permitted to enroll to phase 2/expansion
             phase only with investigator approval).

          -  Aspartate aminotransferase (AST) =< 2.5 x ULN and alanine aminotransferase (ALT) =<
             2.5 x ULN.

          -  Serum creatinine =<1.5 x ULN (If serum creatinine is > 1.5 mg/dL, calculated
             creatinine clearance > 50 mL/min using the Cockcroft-Gault formula may be included).

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L.

          -  Platelet count >= 100,000/mm^3 (100 x 10^9/L).

          -  Hemoglobin >= 9 g/dL.

          -  Serum triglyceride =< 300 mg/dL.

          -  Serum cholesterol =< 350 mg/dL.

          -  Baseline cardiac left ventricular ejection fraction (LVEF) within institutional limits
             of normal (by echocardiogram or multigated acquisition [MUGA] study).

          -  Baseline electrocardiogram with corrected QT (QTc) < 480 millisecond.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          -  Male or non-pregnant and non-breast feeding female:

               -  Females of child-bearing potential must agree to use highly effective
                  contraception without interruption from initiation of therapy and while on study
                  medication and have a negative serum pregnancy test (beta human chorionic
                  gonadotropin [beta-hCG]) result at screening and agree to ongoing pregnancy
                  testing during the course of the study, and at the end of study treatment. A
                  highly effective method of contraception is defined as one that results in a low
                  failure rate (that is, < 1% per year), when used consistently and correctly, such
                  as implants, injectables, combined oral contraceptives, some intrauterine
                  contraceptive devices, sexual abstinence, or a vasectomized partner.

               -  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.

          -  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:

          -  Soft tissue sarcomas with biology or defined treatments for which pazopanib is not
             indicated, including adipocytic STS, gastrointestinal stromal tumors (GIST), or
             Kaposi's sarcoma.

          -  Previously received an mTOR inhibitor or angiogenesis inhibitor.

          -  Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A
             subject 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.

          -  Subjects with hemoptysis, central nervous system hemorrhage or gastrointestinal
             hemorrhage within the last 6 months prior to treatment are excluded due to
             pazopanib-associated risk of bleeding.

          -  Subjects with severe hepatic impairment and active gastrointestinal bleeding.

          -  Uncontrolled serious medical or psychiatric illness.

          -  Subjects with a currently active second malignancy other than non-melanoma skin
             cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or
             other adequately treated carcinoma-in-situ are ineligible. Subjects 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).

          -  No clinically significant gastrointestinal abnormalities including malabsorption
             syndrome, major resection of the stomach or small bowel that could affect the
             absorption of study drug, active peptic ulcer disease, inflammatory bowel disease,
             ulcerative colitis, or other gastrointestinal conditions with increased risk of
             perforation, history of abdominal fistula, gastrointestinal perforation, or
             intra-abdominal abscess within 28 days prior to beginning study treatment.

          -  Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HbA1c) > 8% despite
             adequate therapy.

          -  Subjects with unstable coronary artery disease, myocardial infarction, or an arterial
             thromboembolic event during preceding 6 months.

          -  Subjects 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, terfenadine) within the 14 days prior to
             receiving the first dose of ABI-009.

          -  Active hepatitis B or hepatitis C infection.

          -  Systemic immunosuppression, including human immunodeficiency virus (HIV) positive
             status with or without acquired immunodeficiency syndrome (AIDS).

          -  Subjects with history of intestinal perforations, fistula, hemorrhages and/or
             hemoptysis =< 6 months prior to first study treatment.

          -  Subjects with hypercholesterolemia receiving ongoing treatment with simvastatin.

          -  Subjects who have had major surgery within 28 days of planned initiation of protocol
             therapy, or patients who have/have had wound dehiscence, or other open wounds
             (including diabetic or infectious wounds) with active wound complications.

          -  Subjects with prior history of severe hypersensitivity (grade 3 or higher) to any
             known drug excipients, including anaphylaxis to human serum albumin.

          -  Subjects with uncontrolled hypertension, defined as an average systolic blood pressure
             (SBP) >= 140 mmHg or an average diastolic blood pressure (DBP) >= 90 mmHg despite best
             supportive care measures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum-tolerated dose (MTD) of nab-rapamycin in combination with pazopanib (Phase I)
Time Frame:Up to 21 days
Safety Issue:
Description:Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.

Secondary Outcome Measures

Measure:Incidence of adverse events profile (Phase I and II)
Time Frame:Up to 28 days after last dose
Safety Issue:
Description:Will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measure:Median overall survival (OS) (Phase II)
Time Frame:At 12 months
Safety Issue:
Description:Will be summarized using Kaplan-Meier (KM) analysis and descriptive statistics.
Measure:Median PFS (Phase II)
Time Frame:At 6 months
Safety Issue:
Description:Will be summarized using KM analysis and descriptive statistics.
Measure:Disease control rate (complete response [CR] +partial response [PR] + stable disease [SD]) (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be based on RECIST v1.1. Will be evaluated by computed tomography (CT) imaging.
Measure:Duration of response (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be evaluated by CT imaging.
Measure:Objective response rate (CR + PR) (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be based on RECIST v1.1. Will be evaluated by CT imaging.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

March 25, 2020