Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

• Sponsor: NRG Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT02728258
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 11
• Locations: 43
• Arm: 1
• Actual Duration (Months): 40.9
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Cancer	Drug: Copanlisib; Other: Laboratory Biomarker Analysis	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 16, 2016
• Actual Primary Completion Date: Aug 18, 2018
• Actual Study Completion Date: Feb 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Copanlisib; Given IV; Other Names: BAY 80-6946 PI3K Inhibitor BAY 80-6946 ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Frequency of Objective Response Defined by RECIST 1.1 Criteria [approximate study duration 1 year 9 months]

   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

Secondary Outcome Measures

1. Percentage of Participants Alive and Progression-free at 6 Months [Up to 6 months from enrollment]

   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

2. Median Progression-Free Survival Using RECIST 1.1 Criteria [Up to 2 years from enrollment]

   The median progression-free survival time

3. Median Overall Survival [up to 2 years from enrollment]

   Median time of overall survival

4. The Frequency and Severity of CTCAE v4 Graded Adverse Events [approximately 1 year 9 months]

   Maximum grade of physician assessed adverse events reported during treatment

Other Outcome Measures

1. Mutation Subtypes and Clinical Outcomes [Up to 5 years]

   Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06520
2	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida	United States	33442
3	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
4	Northside Hospital	Atlanta	Georgia	United States	30342
5	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
6	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
7	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
8	Crossroads Cancer Center	Effingham	Illinois	United States	62401
9	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
10	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
11	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
12	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
13	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
14	Baystate Medical Center	Springfield	Massachusetts	United States	01199
15	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
16	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
17	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
18	Billings Clinic Cancer Center	Billings	Montana	United States	59101
19	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
20	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
21	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
22	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
23	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
24	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
25	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
26	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
27	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
28	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
29	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
30	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
31	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
32	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
33	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
34	Women and Infants Hospital	Providence	Rhode Island	United States	02905
35	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
36	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
37	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
38	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
39	Parkland Memorial Hospital	Dallas	Texas	United States	75235
40	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
41	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
42	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
43	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin	United States	54482

Sponsors and Collaborators

• NRG Oncology
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Alessandro D Santin, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 21, 2017

More Information

Publications

None provided.

• Responsible Party: NRG Oncology
• ClinicalTrials.gov Identifier: NCT02728258
• Other Study ID Numbers: NRG-GY008; NCI-2016-00325; NRG-DT1419; NRG-GY008; NRG-GY008; NRG-GY008; U10CA180868
• First Posted: Apr 5, 2016
• Last Update Posted: Feb 15, 2022
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Recurrence

Study Results

Participant Flow

Recruitment Details	The study was activated 9/16/2016 and the last patient was enrolled in May 2017. The study was officially closed to accrual on 8/7/2017 after the first stage of accrual was completed and all screened patients were either enrolled or refused. The study did not continue on to the second stage of accrual.
Pre-assignment Detail	Tumor samples were screened for somatic "hotspot" PIK3CA gene mutations prior to enrollment.

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Overall Participants	11
Age, Customized (Count of Participants)
50-59 years	3 27.3%
60-69 years	4 36.4%
70-79 years	4 36.4%
Sex: Female, Male (Count of Participants)
Female	11 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 9.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 90.9%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Frequency of Objective Response Defined by RECIST 1.1 Criteria
Description	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
Time Frame	approximate study duration 1 year 9 months

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Measure Participants	11
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

2. Secondary Outcome

Title	Percentage of Participants Alive and Progression-free at 6 Months
Description	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
Time Frame	Up to 6 months from enrollment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Measure Participants	11
Number [percentage of participants]	27 245.5%

3. Secondary Outcome

Title	Median Progression-Free Survival Using RECIST 1.1 Criteria
Description	The median progression-free survival time
Time Frame	Up to 2 years from enrollment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Measure Participants	11
Median (95% Confidence Interval) [Months]	2.8

4. Secondary Outcome

Title	Median Overall Survival
Description	Median time of overall survival
Time Frame	up to 2 years from enrollment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Measure Participants	11
Median (95% Confidence Interval) [Months]	15.2

5. Secondary Outcome

Title	The Frequency and Severity of CTCAE v4 Graded Adverse Events
Description	Maximum grade of physician assessed adverse events reported during treatment
Time Frame	approximately 1 year 9 months

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Copanlisib
Arm/Group Description	IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle)
Measure Participants	11
Grade 1	1 9.1%
Grade 2	1 9.1%
Grade 3	7 63.6%
Grade 4	2 18.2%
Grade 5	0 0%

6. Other Pre-specified Outcome

Title	Mutation Subtypes and Clinical Outcomes
Description	Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Assessed throughout the treatment period and up to 4 weeks after discontinuation of treatment
Arm/Group Title	Treatment (Copanlisib)
Arm/Group Description	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: Given IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Copanlisib)
	Affected / at Risk (%)	# Events
Total	7/11 (63.6%)
Serious Adverse Events
	Treatment (Copanlisib)
	Affected / at Risk (%)	# Events
Total	4/11 (36.4%)
Blood and lymphatic system disorders
Anemia	1/11 (9.1%)	1
Infections and infestations
Cellulitis (other)	1/11 (9.1%)	1
Metabolism and nutrition disorders
Hyperglycemia	2/11 (18.2%)	2
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Copanlisib)
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anemia	3/11 (27.3%)	3
Gastrointestinal disorders
Abdominal Pain	4/11 (36.4%)	4
Constipation	4/11 (36.4%)	4
Rectal Pain	1/11 (9.1%)	1
Gastroparesis	1/11 (9.1%)	1
Mucositis Oral	3/11 (27.3%)	3
Nausea	4/11 (36.4%)	4
Oral Dysesthesia	1/11 (9.1%)	1
Rectal Hemorrhage	1/11 (9.1%)	1
Toothache	1/11 (9.1%)	1
Vomiting	4/11 (36.4%)	4
General disorders
Chills	1/11 (9.1%)	1
Edema Limbs	1/11 (9.1%)	1
Fatigue	6/11 (54.5%)	6
Fever	1/11 (9.1%)	1
Infusion Related Reaction	2/11 (18.2%)	2
Localized Edema	1/11 (9.1%)	1
Non-Cardiac Chest Pain	1/11 (9.1%)	1
Infections and infestations
Sinusitis	1/11 (9.1%)	1
Skin Infection	2/11 (18.2%)	2
Investigations
Cholesterol High	1/11 (9.1%)	1
Creatinine Increased	1/11 (9.1%)	1
Lymphocyte Count Decreased	1/11 (9.1%)	1
Neutrophil Count Decreased	3/11 (27.3%)	3
White Blood Cell Decreased	1/11 (9.1%)	1
Metabolism and nutrition disorders
Anorexia	1/11 (9.1%)	1
Hyperglycemia	3/11 (27.3%)	3
Hypertriglyceridemia	1/11 (9.1%)	1
Hypoalbuminemia	1/11 (9.1%)	1
Hypomagnesemia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/11 (9.1%)	1
Arthritis	1/11 (9.1%)	1
Back Pain	3/11 (27.3%)	3
Flank Pain	1/11 (9.1%)
Pain in Extremity	1/11 (9.1%)
Nervous system disorders
Dizziness	1/11 (9.1%)
Headache	2/11 (18.2%)
Peripheral Sensory Neuropathy	1/11 (9.1%)
Syncope	1/11 (9.1%)
Psychiatric disorders
Anxiety	1/11 (9.1%)
Insomnia	1/11 (9.1%)
Renal and urinary disorders
Bladder Spasm	1/11 (9.1%)
Urinary Incontinence	1/11 (9.1%)
Urinary Urgency	1/11 (9.1%)
Reproductive system and breast disorders
Vaginal Discharge	1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis	1/11 (9.1%)
Cough	2/11 (18.2%)
Epistaxis	1/11 (9.1%)
Nasal Congestion	1/11 (9.1%)
Sore Throat	1/11 (9.1%)
Skin and subcutaneous tissue disorders
Bullous Dermatitis	1/11 (9.1%)
Pruritus	1/11 (9.1%)
Rash Maculo-Papular	4/11 (36.4%)
Vascular disorders
Hypertension	2/11 (18.2%)

Limitations/Caveats

The study did not continue on to the second stage of accrual.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.