Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

NCT ID: NCT02728258

Last Updated: 2022-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-16
• Study Completion Date: 2020-02-14

Brief Summary

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.

Conditions

Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (copanlisib)

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.

Group Type: EXPERIMENTAL

Copanlisib

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Copanlisib

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BAY 80-6946; PI3K Inhibitor BAY 80-6946

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 agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug
• 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 a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions
• 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 registration
• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration
• 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 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration
• 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
• Completion of pre-study protocol specific assessments as required
• Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration
• 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 must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
• Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry
• Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry
• Note: ULN is institutional or laboratory upper limit of normal
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; 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

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 II
• Myocardial infarction or unstable angina less than 6 months before registration
• 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 registration
• 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 active HBV or hepatitis C infection are not eligible for enrollment; 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 registration
• Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h
• 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
• Strong 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
• Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies
• Concomitant radiotherapy
• Women who are breast feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro D Santin

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Yale University

New Haven, Connecticut, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Northside Hospital

Atlanta, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

Crossroads Cancer Center

Effingham, Illinois, United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Cancer Care Center of O'Fallon

O'Fallon, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, United States

Baystate Medical Center

Springfield, Massachusetts, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

Delbert Day Cancer Institute at PCRMC

Rolla, Missouri, United States

Billings Clinic Cancer Center

Billings, Montana, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Southwest Gynecologic Oncology Associates Inc

Albuquerque, New Mexico, United States

Memorial Medical Center - Las Cruces

Las Cruces, New Mexico, United States

State University of New York Downstate Medical Center

Brooklyn, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

The Mark H Zangmeister Center

Columbus, Ohio, United States

ProMedica Flower Hospital

Sylvania, Ohio, United States

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Parkland Memorial Hospital

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Marshfield Clinic Stevens Point Center

Stevens Point, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2016-00325

Identifier Type: REGISTRY

Identifier Source: secondary_id

NRG-DT1419

Identifier Type: -

Identifier Source: secondary_id

NRG-GY008

Identifier Type: -

Identifier Source: secondary_id

NRG-GY008

Identifier Type: OTHER

Identifier Source: secondary_id

NRG-GY008

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NRG-GY008

Identifier Type: -

Identifier Source: org_study_id