Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer

Endometrial Adenocarcinoma Clinical Trial

Official title:

A Phase II Evaluation of BIBF 1120 in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225887
• Other study ID #: GOG-0229K
• Secondary ID: NCI-2011-02657CD
• Status: Completed
• Phase: Phase 2
• First received: October 20, 2010
• Last updated: September 8, 2017
• Start date: October 2011
• Est. completion date: January 2016

Study information

• Verified date: October 2016
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies the side effects and how well nintedanib works in treating patients with endometrial cancer that has come back. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

Description:

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with persistent or recurrent endometrial cancer, who survive progression-free without going on a subsequent therapy against the disease for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with BIBF 1120 (nintedanib).

II. To determine the nature and degree of toxicity of BIBF 1120 in this cohort of patients.

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent endometrial cancer treated with BIBF 1120.

OUTLINE:

Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

• 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

• Patient 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 not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population

• Patients must have a GOG performance status of 0, 1, or 2

• Patients must have normal thyroid function; patients with a history of hypothyroidism are eligible, provided it is well controlled on medication

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy

• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection)

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

• Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration

• Any prior radiation therapy must be completed at least 4 weeks prior to registration

• Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; 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 are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease

• Patients must have NOT received any non-cytotoxic (biologic or targeted) agents, as part of their primary treatment or for management of recurrent or persistent disease; non-cytotoxic (biologic or targeted) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction; prior hormonal therapy is allowed; there is no limit on the number of prior hormonal therapies allowed

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

• Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

• Bilirubin must be less than 1.5 X ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than 3 X ULN

• Alkaline phosphatase must be less than 2.5 X ULN

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 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) =< 1.5 times the institutional upper limit of normal

• Electrocardiogram (EKG) must have corrected QT interval (QTc) < 450 msec without evidence of serious ventricular arrhythmia (ventricular tachycardia lasting more than 3 beats or ventricular fibrillation)

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

• Patients must meet pre-entry requirements

• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry; women of child-bearing potential must agree to use adequate contraception (two barrier methods of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she is to inform her treating physician immediately; all patients must be willing to take contraception up to three months after the final dose of BIBF 1120

Exclusion Criteria:

• Patients who have had prior therapy with BIBF 1120

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the start date of treatment; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients with history of brain metastases, or evidence upon physical examination of active central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases

• Uncontrolled hypertension, defined as systolic >= 150 mm Hg or diastolic >= 90 mm Hg

• Myocardial infarction or unstable angina within 6 months of study treatment

• New York Heart Association (NYHA) class II or greater congestive heart failure

• Women with an ejection fraction < institutional lower limit of normal (LLN)

• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)

• Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral vascular disease

• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of study treatment

• Patients undergoing invasive procedures as defined below: major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of treatment; major surgical procedure anticipated during the course of the study; minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of therapy

• Patients who are pregnant or nursing

• Patients with a history of major thromboembolic event defined as: symptomatic pulmonary embolism (PE), recurrent asymptomatic PE, or recurrent deep venous thrombosis

• Prior thrombosis or thromboembolic event due to a known inherited coagulopathy (i.e., antithrombin-III deficiency, protein C or protein S deficiency, factor V Leiden mutation presence, prothrombin G20210A mutation)

• Serious infections requiring systemic antibiotics or antiviral therapy including:

known active hepatitis B or C infection; known human immunodeficiency virus (HIV) infection

• Gastrointestinal (GI) or other medical disorders that would impact ingestion or absorption of the drug

• Patients with a history of photosensitivity or who must take agents which increase photosensitivity, e.g. topical retinoids and doxycycline

• Patients who are unable to swallow capsules

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Mucinous
• Carcinoma
• Carcinoma, Squamous Cell
• Carcinoma, Transitional Cell
• Cystadenocarcinoma
• Endometrial Adenocarcinoma
• Endometrial Clear Cell Adenocarcinoma
• Endometrial Mucinous Adenocarcinoma
• Endometrial Serous Adenocarcinoma
• Endometrial Squamous Cell Carcinoma
• Endometrial Transitional Cell Carcinoma
• Endometrial Undifferentiated Carcinoma
• Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm
• Recurrent Uterine Corpus Carcinoma
• Uterine Neoplasms

Intervention

Drug:
• Nintedanib
Given PO

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Akron General Medical Center	Akron	Ohio
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Carolinas HealthCare System NorthEast	Concord	North Carolina
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Hurley Medical Center	Flint	Michigan
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Saint Vincent Oncology Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Memorial University Medical Center	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Northwest Hospital	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	The incidence of adverse events (grade 3 or higher) as assessed by the National Cancer Institute CTCAE version 4.0	Up to 5 years
Primary	Objective Tumor Response	Complete and Partial Tumor Response by RECIST 1.1	For disease that can be evaluated by physical exam,response was assessed prior to each cycle CT scan or MRI if used to follow lesion for measurable disease every other cycle up to 5 years.
Primary	Progression-free Survival > 6 Months	Whether or not the patient survived progression-free for at least 6 months.	for disease that can be evaluated by physical exam, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle up to 5 years.
Secondary	Overall Survival	The observed length of life from entry into the study to death or the date of last contact.	From study entry to death or last contact, up to 5 years
Secondary	Progression Free Survival	the period of progression free survival for patients with persistent or recurrent endometrial cancer treated with study drug.	The duration of time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years