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Endometrial Endometrioid AdenocarcinomaPhase 2NCT02728258

Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

A Phase 2 study testing Copanlisib and Laboratory Biomarker Analysis in people with Endometrial Endometrioid Adenocarcinoma and Endometrial Mixed Cell Adenocarcinoma, run by NRG Oncology at 43 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Copanlisib and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
43 sitesUnited States
Study dates
16 Sep 2016to 14 Feb 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Southwest Gynecologic Oncology Associates Inc

    Albuquerque, New Mexico, 87106

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • State University of New York Downstate Medical Center

    Brooklyn, New York, 11203

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Memorial Medical Center - Las Cruces

    Las Cruces, New Mexico, 88011

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06520

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Delbert Day Cancer Institute at PCRMC

    Rolla, Missouri, 65401

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

    Savannah, Georgia, 31405

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Marshfield Clinic Stevens Point Center

    Stevens Point, Wisconsin, 54482

  • ProMedica Flower Hospital

    Sylvania, Ohio, 43560

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

  • Oklahoma Cancer Specialists and Research Institute-Tulsa

    Tulsa, Oklahoma, 74146

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Copanlisib, Laboratory Biomarker Analysis
Medical subject headings
Carcinoma, Endometrioid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CopanlisibDrug

    Also called BAY 80-6946, PI3K Inhibitor BAY 80-6946

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02728258
Study groupRoleWhat they receive
Treatment (copanlisib)ExperimentalPatients 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.
Receives: Drug: Copanlisib; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of Objective Response Defined by RECIST 1.1 Criteria

    Confirmed complete and partial tumor response by RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Measured: approximate study duration 1 year 9 months

Secondary outcomes (4)

  1. Percentage of Participants Alive and Progression-free at 6 Months

    Percentage of participants who are progression free at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: Up to 6 months from enrollment

  2. Median Progression-Free Survival Using RECIST 1.1 Criteria

    The median progression-free survival time

    Measured: Up to 2 years from enrollment

  3. Median Overall Survival

    Median time of overall survival

    Measured: up to 2 years from enrollment

  4. The Frequency and Severity of CTCAE v4 Graded Adverse Events

    Maximum grade of physician assessed adverse events reported during treatment

    Measured: approximately 1 year 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2016 (estimated)
  2. Study start16 Sep 2016
  3. Primary completion18 Aug 2018
  4. Study completion14 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02728258
Sponsor's protocol ID
NRG-GY008
Other IDs
NCI-2016-00325, NRG-DT1419, NRG-GY008, NRG-GY008, NRG-GY008, U10CA180868
Status last verified
Nov 2021
First submitted
30 Mar 2016
Last updated
15 Feb 2022
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Copanlisib and Laboratory Biomarker Analysis in people with Endometrial Endometrioid Adenocarcinoma and Endometrial Mixed Cell Adenocarcinoma, run by NRG Oncology at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Objective Response Defined by RECIST 1.1 Criteria (time frame: approximate study duration 1 year 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02728258.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2022.

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