Clinical Trials /

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

NCT02646319

Description:

This pilot trial studies how well nanoparticle albumin-bound rapamycin works in treating patients with cancer that as has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced cancer) and that has an abnormality in a protein called mechanistic target of rapamycin (mTOR). Patients with this mutation are identified by genetic testing. Patients then receive nanoparticle albumin-bound rapamycin, which may stop the growth of cancer cells by blocking the mTOR enzyme, which is needed for cell growth and multiplication. Using treatments that target a patient's specific mutation may be a more effective treatment than the standard of care treatment.

Related Conditions:
  • Cancer
Recruiting Status:

Completed

Phase:

Early Phase 1

Trial Eligibility

Document

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With <span class="go-doc-concept go-doc-biomarker">mTOR</span> <span class="go-doc-concept go-doc-keyword">Mutations</span>

Title

  • Brief Title: Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations
  • Official Title: A Pilot Study of a Rapid Access Platform for Investigational Drugs (RAPID) in Advanced Cancers
  • Clinical Trial IDs

    NCT ID: NCT02646319

    ORG ID: MC1313

    NCI ID: NCI-2015-02151

    Trial Conditions

    Adult Solid Neoplasm

    Advanced Malignant Neoplasm

    Cervical Squamous Cell Carcinoma

    Recurrent Bladder Carcinoma

    Recurrent Breast Carcinoma

    Recurrent Cervical Carcinoma

    Recurrent Head and Neck Carcinoma

    Recurrent Malignant Neoplasm

    Recurrent Ovarian Carcinoma

    Recurrent Renal Cell Carcinoma

    Recurrent Uterine Corpus Carcinoma

    Sarcoma

    Stage III Bladder Cancer

    Stage III Renal Cell Cancer

    Stage IIIA Breast Cancer

    Stage IIIA Cervical Cancer

    Stage IIIA Ovarian Cancer

    Stage IIIA Uterine Corpus Cancer

    Stage IIIB Breast Cancer

    Stage IIIB Cervical Cancer

    Stage IIIB Ovarian Cancer

    Stage IIIB Uterine Corpus Cancer

    Stage IIIC Breast Cancer

    Stage IIIC Ovarian Cancer

    Stage IIIC Uterine Corpus Cancer

    Stage IIIC1 Uterine Corpus Cancer

    Stage IIIC2 Uterine Corpus Cancer

    Stage IV Breast Cancer

    Stage IV Ovarian Cancer

    Stage IV Renal Cell Cancer

    Stage IVA Bladder Cancer

    Stage IVA Cervical Cancer

    Stage IVA Uterine Corpus Cancer

    Stage IVB Bladder Cancer

    Stage IVB Cervical Cancer

    Stage IVB Uterine Corpus Cancer

    Trial Interventions

    Drug Synonyms Arms
    Nanoparticle Albumin-Bound Rapamycin ABI-009, Nab-Rapamycin Treatment (nanoparticle albumin-bound rapamycin)

    Trial Purpose

    This pilot phase II trial studies how well nanoparticle albumin-bound rapamycin works in
    treating patients with cancer that as has spread to other places in the body and usually
    cannot be cured or controlled with treatment (advanced cancer) and that has an abnormality
    in a protein called mechanistic target of rapamycin (mTOR). Patients with this mutation are
    identified by genetic testing. Patients then receive nanoparticle albumin-bound rapamycin,
    which may stop the growth of cancer cells by blocking the mTOR enzyme, which is needed for
    cell growth and multiplication. Using treatments that target a patient's specific mutation
    may be a more effective treatment than the standard of care treatment.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To investigate efficacy of groups of patients defined by disease type, genomic aberration
    and treatment regimen.

    II. To assess the confirmed response rate of nanoparticle albumin-bound rapamycin
    (nab-rapamycin) in mammalian target of rapamycin (mTOR) aberrant advanced cancers.
    (Sub-protocol Arm A)

    SECONDARY OBJECTIVES:

    I. To estimate other clinical outcomes (e.g., progression-free and overall survival) of
    groups of patients defined by disease type, genomic aberration and treatment regimen.

    II. To describe the adverse event profile of each regimen. III. To assess the clinical
    benefit rate of nab-rapamycin in mTOR aberrant advanced cancers. (Sub-protocol Arm A).

    IV. To estimate progression-free survival (specifically at 6 months) and overall survival of
    these patients. (Sub-protocol Arm A) V. To estimate the adverse event profile of
    nab-rapamycin. (Sub-protocol Arm A)

    TERTIARY OBJECTIVES:

    I. To describe patient health-related quality of life (HRQOL) and symptoms using the
    European Organization for Research and Treatment of Cancer (EORTC) Quality of Life
    Questionnaire-Core (QLQ-C)30 in groups of patients defined by disease type and/or treatment
    regimen and to correlative HRQOL/symptoms with genomic markers.

    II. To assess the rate of individual mTOR pathway aberrations and assess the association
    between individual mTOR pathway aberrations and clinical outcome both across disease
    indications and within disease indications. (Sub-protocol Arm A)

    OUTLINE:

    Patients receive nanoparticle albumin-bound rapamycin intravenously (IV) over 30 minutes on
    days 1 and 8. Treatment repeats every 21 days for 24 weeks in the absence of disease
    progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up periodically.

    Trial Arms

    Name Type Description Interventions
    Treatment (nanoparticle albumin-bound rapamycin) Experimental Patients receive nanoparticle albumin-bound rapamycin IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 24 weeks in the absence of disease progression or unacceptable toxicity. Nanoparticle Albumin-Bound Rapamycin

    Eligibility Criteria

    Inclusion Criteria:

    - Histologic proof of cancer which is now not amenable to curative standard treatment
    options

    - Patient must have received at least 1 prior standard therapy for their disease

    - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

    - Ability to provide informed written consent

    - Willing to return to enrolling institution for follow-up (Active Monitoring Phase of
    the study); Note: During the Active Monitoring Phase of a study (i.e., active
    treatment), participants must be willing to return to the consenting institution for
    follow-up

    - Life expectancy >= 84 days (3 months)

    - Identification of a drug target/targets through molecular profiling performed as a
    part of routine clinical care and treatment recommendation by the Mayo Clinic
    Genomics Tumor Board (GTB); NOTE: If profile matches more than 1 treatment arm, final
    decision for treatment arm assignment to be made by patients treating physician; it
    will be required for the genomic aberration to be identified through a test in a
    Clinical Laboratory Improvement Amendments (CLIA) workflow; assays used will range
    from single gene abnormalities (e.g. fluorescent in situ hybridization [FISH] for
    human epidermal growth factor receptor 2 [ERBB2] amplifications) to next generation
    sequencing based gene panels (Foundation One) to more comprehensive assays such as
    whole exome sequencing; the Mayo Clinic GTB will serve as the centralized point of
    data synthesis to allow for assessment of molecular profiling accomplished through a
    heterogeneous array of tests

    - Date of Mayo Clinic Genomics Tumor Board review =< 3 months prior to registration

    - Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version
    (v)1.1 criteria (for solid tumors) or equivalent criteria (for patients with
    non-solid tumor malignancies)

    - Patient meets all sub-protocol specific criteria of each applicable sub-protocol

    - Ability to complete questionnaire(s) by themselves or with assistance

    - SUB-PROTOCOL AIM A: Histological confirmation of renal cell carcinoma, head and neck
    cancer, endometrial cancer, breast cancer, ovarian cancer, sarcoma, squamous cell
    cervical or uterine cancer, or bladder cancer

    - SUB-PROTOCOL AIM A: Confirmation of advanced cancer with mTOR pathway aberrations as
    determined through routine clinical care using pathway aberrations performed in a
    CLIA certified laboratory; cancer genomic profiling tests incorporating next
    generation sequencing from archival formalin-fixed paraffin-embedded tissue (FFPE)
    are validated with sensitivities and specificities of 99% and 99%, respectively; in
    the assay, hybrid-capture-selected deoxyribonucleic acid (DNA) libraries are
    sequenced to depths targeting > 500 coverage by non-polymerase chain reaction (PCR)
    duplicate read pairs, with > 99% of exons at coverage > 100); multiplatform
    profiling may include immunohistochemistry and in situ hybridization methods with
    previously established negative/positive cutoffs performed in a CLIA certified lab;
    at least one pathway aberration must be identified; these must be confirmed in a CLIA
    certified lab; the potential mTOR aberrations that could be identified are listed
    below, please note that this list is not all inclusive; if a CLIA validated report
    lists an mTOR pathway inhibitor as a target drug for a genetic aberration, then it
    can be considered eligible for the purposes of this study; v-akt murine thymoma viral
    oncogene homolog 1 (AKT1), MTOR, phosphatidylinositol-4,5-bisphosphate 3-kinase,
    catalytic subunit alpha (PIK3CA), tuberous sclerosis (TSC)1, TSC2,
    retrovirus-associated DNA sequence (Ras) homolog enriched in brain (RHEB),
    serine/threonine kinase 11 (STK11), neurofibromin (NF)1/2

    - SUB-PROTOCOL AIM A: Absolute neutrophil count (ANC) >= 1500/mm^3

    - SUB-PROTOCOL AIM A: Platelet count >= 100,000/mm^3

    - SUB-PROTOCOL AIM A: Hemoglobin >= 9.0 g/dL

    - SUB-PROTOCOL AIM A: Total bilirubin =< 1.5 x institutional upper limit of normal
    (ULN)

    - SUB-PROTOCOL AIM A: Aspartate transaminase (AST); alanine aminotransferase (ALT) =<
    1.5 x ULN; NOTE: if subject has tumor involvement in the liver =< 5 X ULN

    - SUB-PROTOCOL AIM A: Serum cholesterol =< 350 mg/dL

    - SUB-PROTOCOL AIM A: Serum triglyceride =< 300 mg/dL

    - SUB-PROTOCOL AIM A: Serum creatinine =< 1.5 x ULN

    - SUB-PROTOCOL AIM A: Previously treated patients who have failed, unable to tolerate,
    or refused other available active therapies

    - SUB-PROTOCOL AIM A: Women of child-bearing potential, defined as sexually mature
    women who have not undergone a hysterectomy or who have not been naturally
    postmenopausal for at least 12 consecutive months (e.g., who has had menses any time
    in the preceding 12 consecutive months), must have a negative serum pregnancy test =<
    14 days prior to registration and must use two forms of highly effective
    contraception (also applicable to their partners who are biologically able to
    conceive)

    - SUB-PROTOCOL AIM A: Adequate coagulation function as defined by either of the
    following criteria:

    - International normalized ratio (INR) =< 1.5 x ULN

    - For subjects receiving warfarin or low molecular weight heparin (LMWH), the
    subjects must, in the investigator's opinion, be clinically stable with no
    evidence of active bleeding while receiving anticoagulant therapy; the INR for
    these patients may exceed 1.5 x ULN if that is the goal of the anticoagulant
    therapy

    Exclusion Criteria:

    - Uncontrolled intercurrent illness including, but not limited to: ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements

    - Failure to fully recover from acute, reversible effects of prior chemotherapy (other
    anti-neoplastic therapy) and radiation therapy to adverse event severity of =< grade
    1

    - Co-morbid systemic illnesses or other severe concurrent disease which, in the
    judgment of the investigator, would make the patient inappropriate for entry into
    this study or interfere significantly with the proper assessment of safety and
    toxicity of the prescribed regimens

    - SUB-PROTOCOL AIM A: Any of the following:

    - Pregnant women

    - Nursing women

    - Women of child-bearing potential, who are biologically able to conceive, or men
    who are able to father a child, not employing two forms of highly effective
    contraception

    - Highly effective contraception (e.g., male condom with spermicide,
    diaphragm with spermicide, intra-uterine device, and total abstinence) must
    be used by both sexes during the study and must be continued for 6 months
    after the end of study treatment; Note: Oral, implantable, or injectable
    hormone contraceptives are not considered effective for this study

    - SUB-PROTOCOL AIM A: Any of the following treatments:

    - Chemotherapy within 4 weeks before treatment with nab-rapamycin

    - Hormonal therapy within 4 weeks before treatment with nab-rapamycin (with the
    exception of leuprolide, degarelix, or goserelin)

    - Immunotherapy within 4 weeks before treatment with nab-rapamycin

    - Radiotherapy within 4 weeks before treatment with nab-rapamycin

    - Treatment with nitrosoureas, mitomycin, or extensive radiotherapy within 6 weeks
    before treatment with nab-rapamycin

    - Immunosuppressive agents within 3 weeks before treatment with nab-rapamycin
    (except corticosteroids used as antiemetics)

    - Use of prior mTOR pathway inhibitor therapy

    - SUB-PROTOCOL AIM A: Patients with a history of interstitial lung disease and/or
    pneumonia

    - SUB-PROTOCOL AIM A: Receiving any concomitant antitumor therapy or inhibitors of
    cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)

    - SUB-PROTOCOL AIM A: History of allergic reactions attributed to compounds of similar
    chemical or biologic composition including macrolide (e.g. azithromycin,
    clarithromycin, dirithromycin, and erythromycin) and ketolide antibiotics

    - SUB-PROTOCOL AIM A: Major surgery (e.g., intra-thoracic, intra-abdominal or
    intra-pelvic) =< 4 weeks prior to registration or failure to recover from side
    effects of such surgery; exceptions: port placements, nephrectomy, tumor biopsies,
    and minor surgeries

    - SUB-PROTOCOL AIM A: Concurrent use of any other approved or investigational
    anticancer agents which would be considered as a treatment for the primary neoplasm

    - SUB-PROTOCOL AIM A: Patients with a history of alcoholism, drug addiction or
    psychotic disorders

    - SUB-PROTOCOL AIM A: Uncontrolled diabetes mellitus as defined by hemoglobin A1C
    (HbA1c) > 8% despite adequate therapy; unstable coronary artery disease or myocardial
    infarction during preceding 6 months; or hypertension uncontrolled by medication

    - SUB-PROTOCOL AIM A: Patients who required therapeutic doses of anticoagulants

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Proportion of confirmed responses, evaluated using the RECIST v1.1

    Secondary Outcome Measures

    Clinical benefit rate defined as the proportion of patients with a confirmed response or stable disease (complete response+partial response+stable disease) divided by the total number of evaluable patients

    Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0

    Quality of life, measured using the EORTC QLQ-C30

    Rate of individual mTOR pathway aberrations

    Survival time

    Time to disease progression

    Trial Keywords