Clinical Trials /

Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

NCT02728258

Description:

This phase II trial studies how well copanlisib works in treating patients with endometrial cancer that has not decreased or disappeared, and the cancer may still be in the body despite treatment (persistent) or has come back (recurrent). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Copanlisib</span> in Treating Patients With Persistent or Recurrent Endometrial Cancer

Title

  • Brief Title: Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer
  • Official Title: A Phase II Evaluation of Copanlisib (BAY 80-6946), a Selective Inhibitor of PI3KCA, in Patients With Persistent or Recurrent Endometrial Carcinoma Harboring PIK3CA Hotspot Mutations
  • Clinical Trial IDs

    NCT ID: NCT02728258

    ORG ID: NRG-GY008

    NCI ID: NCI-2016-00325

    Trial Conditions

    Endometrial Endometrioid Adenocarcinoma

    Endometrial Mixed Adenocarcinoma

    Endometrial Serous Adenocarcinoma

    Endometrial Undifferentiated Carcinoma

    Metastatic Endometrioid Adenocarcinoma

    Recurrent Uterine Corpus Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Copanlisib BAY 80-6946, PI3K Inhibitor BAY 80-6946 Treatment (copanlisib)

    Trial Purpose

    This phase II trial studies how well copanlisib works in treating patients with endometrial
    cancer that has not decreased or disappeared, and the cancer may still be in the body
    despite treatment (persistent) or has come back (recurrent). Copanlisib may stop the growth
    of tumor cells by blocking some of the enzymes needed for cell growth.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To assess the activity of copanlisib (BAY 80-6946) in patients with persistent or
    recurrent endometrial carcinoma harboring phosphatidylinositol-4,5-bisphosphate 3-kinase,
    catalytic subunit alpha (PI3KCA) hotspot mutations with the frequency of objective response.

    SECONDARY OBJECTIVES:

    I. To estimate 6 month progression-free survival (PFS) and median PFS. II. To estimate the
    distribution of the duration of overall survival (OS). III. To assess the safety profile of
    copanlisib in endometrial cancer patients.

    TERTIARY OBJECTIVES:

    I. To systematically evaluate by sequencing the site (i.e., exome) and characteristics of
    PIK3CA mutations in endometrial cancer patients and correlate such mutations to overall
    response (OR), PFS, and OS in patients treated with copanlisib.

    OUTLINE:

    Patients receive copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15. Courses
    repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up every 3 months for 2 years and
    then every 6 months for 3 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (copanlisib) Experimental Patients receive copanlisib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Copanlisib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have the psychological ability and general health that permits
    completion of the study requirements and required follow-up

    - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test
    within 7 days of starting treatment and agree to use adequate contraception when
    sexually active; this applies from the signing of the informed consent form and 12
    months after the last study drug administration

    - Submission of tumor tissue is required for all patients; investigators should check
    with their site pathology department regarding release of biospecimens before
    approaching patients about participation in the trial

    - Patients must have recurrent or persistent endometrial cancer (endometrioid
    adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial
    carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation
    of the primary tumor is required

    - All patients must have PIK3CA gene mutations in a representative primary or
    metastatic tumor sample confirmed by Clinical Laboratory Improvement Amendments
    (CLIA) Roche cobas PIK3CA mutation test

    - All patients must have measurable disease as defined by Response Evaluation Criteria
    in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion
    that can be accurately measured in at least one dimension (longest diameter to be
    recorded); each lesion must be >= 10 mm when measured by computed tomography (CT),
    magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm
    when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when
    measured by CT or MRI

    - Patients must have at least one "target lesion" to be used to assess response on this
    protocol as defined by RECIST 1.1; tumors within a previously irradiated field will
    be designated as 'non-target" lesions unless progression is documented or a biopsy is
    obtained to confirm persistence at least 90 days following completion of radiation
    therapy

    - Patients must have recovered from effects of recent surgery, radiotherapy, or
    chemotherapy; at least 4 weeks must have elapsed since the patient underwent any
    major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for
    minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous
    access device placement)

    - Patients may have received prior radiation therapy for treatment of endometrial
    cancer; prior radiation therapy may have included pelvic radiation therapy, extended
    field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or
    palliative radiation therapy; all radiation therapy must be completed at least 4
    weeks prior to the first date of study therapy

    - Patients may have received prior hormonal therapy for treatment of endometrial
    carcinoma; all hormonal therapy must be discontinued at least one week prior to the
    first date of study therapy

    - Patients may have received prior therapy (including chemotherapy, biologic/targeted
    therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be
    discontinued at least 3 weeks prior to the first date of study therapy; any
    investigational agent must be discontinued at least 30 days prior to the first date
    of study therapy

    - Patients must have had at least one prior chemotherapeutic regimen for management of
    endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and
    radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in
    conjunction with primary radiation as a radio-sensitizer WILL be counted as a
    systemic chemotherapy regimen

    - Patients are allowed to receive, but not required to receive, up to a total of 3
    lines of chemotherapy

    - Appropriate stage for study entry based on the following diagnostic workup:

    - History/physical examination within 28 days prior to registration

    - Imaging of target lesion(s) within 28 days prior to registration

    - Further protocol-specific assessments: central pathology review is being
    performed

    - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2
    within 28 days prior to registration

    - Life expectancy of at least 3 months

    - Absolute neutrophil count (ANC) >= 1,500/mcl

    - Platelets >= 75,000/mcl

    - Hemoglobin (Hgb) >= 8 g/dL

    - Creatinine =< 1.5 x upper limit of normal (ULN)

    - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome)

    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

    - Left ventricular ejection fraction (LVEF) >= 50%

    - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than
    or equal to 300 mg/dl

    - Prothrombin time (PT) such that international normalized ratio (INR) is less than or
    equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a
    stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less
    than or equal to 1.5 times the upper limit of normal

    - The patient or a legally authorized representative must provide study-specific
    informed consent prior to study entry

    - Note: ULN is institutional or laboratory upper limit of normal

    Exclusion Criteria:

    - Patients who have had prior therapy with any phosphatidylinositol 3 kinase
    (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of
    rapamycin (mTor) pathway inhibitor

    - Patients who have the following histologies: mucinous, squamous, sarcomas,
    carcinosarcomas, clear cell

    - Congestive heart failure > New York Heart Association (NYHA) class 2

    - Myocardial infarction or unstable angina less than 6 months before start of
    copanlisib administration

    - Uncontrolled hypertension (systolic blood pressure >= 150 mmHG or diastolic pressure
    >= 90 mmHG despite optimal medical management)

    - Uncontrolled type I or II diabetes mellitus

    - Arterial or venous thrombotic or embolic events such as cerebrovascular accident
    (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
    within 3 months before the start of copanlisib administration

    - Non-healing wound, ulcer or bone fracture

    - Active, clinically serious infections > Common Terminology Criteria for Adverse
    Events (CTCAE) grade 2

    - History of, or current autoimmune disease

    - Human immunodeficiency virus (HIV) infection

    - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV
    up to 28 days prior to study drug start using the routine hepatitis virus
    laboratorial panel; patients with serologic markers of HBV immunization due to known
    vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core
    [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible

    - Previous or concurrent history of malignancies within 5 years prior to study
    treatment except for curatively treated:

    - Cervical carcinoma in situ

    - Non-melanoma skin cancer

    - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and
    T1 [tumor invades lamina propria])

    - Patients with seizure disorder requiring medication

    - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding
    event >= CTCAE grade 3 within 4 weeks prior to the start of study medication

    - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio
    >= 3.5 on a random urine sample)

    - History or concurrent condition of interstitial lung disease of any severity and/or
    severely impaired lung function (as judged by the investigator) concurrent diagnosis
    of pheochromocytoma

    - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior
    therapy/procedure, excluding alopecia

    - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in
    the formulation

    - Cytochrome P450 3A4 (CYP3A4) inhibitors and inducers; concomitant use of strong
    inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir,
    indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin,
    phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within
    two weeks prior to start of study treatment and for the duration of treatment with
    copanlisib

    - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit
    consumption is not permitted during the study

    - Anti-arrhythmic therapy other than beta blockers or digoxin

    - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg
    prednisone or equivalent is not allowed; patients may be using topical or inhaled
    corticosteroids

    - Women of child-bearing potential (WOCBP) must have a negative serous pregnancy test
    within 7 days of starting treatment and agree to use adequate contraception when
    sexually active; this applies from the signing of the informed consent form and 12
    months after the last study drug administration; a woman is considered of
    childbearing potential following menarche and until becoming post-menopausal unless
    permanently sterile; permanent sterilization methods include hysterectomy, bilateral
    salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no
    menses for 12 months without an alternative medical cause; a high follicle
    stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a
    post-menopausal state in women not using hormonal contraception or hormonal
    replacement therapy

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Frequency of objective response defined by RECIST 1.1 criteria

    Secondary Outcome Measures

    Incidence of adverse events of copanlisib using CTCAE version 4.03

    Median PFS using RECIST 1.1 criteria

    OS

    PFS defined using RECIST 1.1 criteria

    Trial Keywords