Ovarian Cancer Clinical Trial
Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer
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.
Full 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.
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
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 41 Locations for this study
New Haven Connecticut, 06520, United States
Deerfield Beach Florida, 33442, United States
Miami Florida, 33136, United States
Atlanta Georgia, 30342, United States
Savannah Georgia, 31405, United States
Decatur Illinois, 62526, United States
Decatur Illinois, 62526, United States
Effingham Illinois, 62401, United States
Geneva Illinois, 60134, United States
O'Fallon Illinois, 62269, United States
Warrenville Illinois, 60555, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50309, United States
Springfield Massachusetts, 01199, United States
Detroit Michigan, 48201, United States
Farmington Hills Michigan, 48334, United States
Rolla Missouri, 65401, United States
Billings Montana, 59101, United States
Omaha Nebraska, 68114, United States
Albuquerque New Mexico, 87102, United States
Albuquerque New Mexico, 87106, United States
Las Cruces New Mexico, 88011, United States
Brooklyn New York, 11203, United States
Buffalo New York, 14263, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43219, United States
Sylvania Ohio, 43560, United States
Toledo Ohio, 43606, United States
Oklahoma City Oklahoma, 73104, United States
Tulsa Oklahoma, 74146, United States
Portland Oregon, 97210, United States
Philadelphia Pennsylvania, 19104, United States
Pittsburgh Pennsylvania, 15232, United States
Providence Rhode Island, 02905, United States
Greenville South Carolina, 29605, United States
Seneca South Carolina, 29672, United States
Rapid City South Dakota, 57701, United States
Sioux Falls South Dakota, 57105, United States
Dallas Texas, 75235, United States
Dallas Texas, 75390, United States
Falls Church Virginia, 22042, United States
Marshfield Wisconsin, 54449, United States
Stevens Point Wisconsin, 54482, United States
How clear is this clinincal trial information?

Please confirm you are a US based health care provider:
Yes, I am a health care Provider No, I am not a health care providerSign Up Now.
Take Control of Your Disease Journey.
Sign up now for expert patient guides, personalized treatment options, and cutting-edge insights that can help you push for the best care plan.