BIBF 1120 in Bevacizumab Resistant, Persistent, or Recurrent Epithelial Ovarian Cancer

• Sponsor: AA Secord (Other)
• Overall Status: Completed
• CT.gov ID: NCT01669798
• Collaborator: Boehringer Ingelheim (Industry)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Duration (Months): 60
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to see if BIBF 1120 can increase the number of women with bevacizumab resistant, persistent, or recurrent epithelial ovarian cancer who do not progress for at least six months.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer	Drug: BIBF 1120	Phase 2

Detailed Description

Ovarian cancer patients with platinum-resistant and refractory disease have the lowest response rates to relapse chemotherapy: various chemotherapeutic agents, such as paclitaxel, liposomal doxorubicin, topotecan, docetaxel, platinum, etoposide, ifosfamide, gemcitabine, and vinorelbine are available but result in response rates of 7-40%. Unfortunately, relapse therapy is not curative and treatment is only palliative. Recently two phase II trials demonstrated that anti-angiogenic therapy with bevacizumab alone or in combination with chemotherapy in women with recurrent disease had response rates ranging from 16-24% with an acceptable toxicity profile. However, resistance can develop to VEGF inhibition. Therefore other novel anti-angiogenic agents, such as BIBF 1120, should be evaluated in the treatment of ovarian cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Evaluation of BIBF 1120 in the Treatment of Bevacizumab-Resistant, Persistent, or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Sep 10, 2017
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BIBF 1120 BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy.	Drug: BIBF 1120; PO 200mg BID; Other Names: Vargatef™ Nintedanib

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Who Survive Progression-free [6 months]

   Measure of Progression Free Survival (PFS) by the percentage of patients who survive progression-free for at least 6 months after initiating study therapy in patients with bevacizumab-resistant, persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

Secondary Outcome Measures

1. Objective Tumor Response Via RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 [1 year]

   Evaluating the percentage of patients who have objective tumor response (complete or partial) based on RECIST 1.1 criteria.

2. Duration of Progression-Free Survival [Through study completion, on average 2 years]

   The duration of progression-free survival and overall survival measured in months; Progression-Free Survival (PFS) is defined as the duration of time from study entry to time of progression or death, whichever occurs first.

3. Objective Tumor Response Based on GCIG CA-125 Criteria [1 year]

   The proportion of patients who have objective tumor response (complete or partial) based on Gynaecologic Cancer InterGroup(GCIG) CA-125 criteria which is: "A response according to CA 125 has occurred if there is at least a 50% reduction in CA 125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days.".

4. Adverse Event Frequency and Severity [1 year]

   To determine frequency and severity of adverse events as assessed using NCI Common Toxicity Criteria version 4.

Other Outcome Measures

1. Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response [1 year]

   Correlating baseline and on treatment levels of additional growth factors measured in picograms per milliliter that may be co- or counter- regulated with VEGF with response to treatment

2. Coagulation and Endothelial Cell Activation Markers [1 year]

   To measure baseline and on treatment levels of additional growth factors that may be co- or counter- regulated with VEGF and correlate with response to treatment.

3. VEGF Levels Correlated With Treatment Outcome [1 year]

   Baseline levels of VEGF were correlated with treatment outcome. Results are stratified in groups: "Partial Response (PR) or Stable Disease (SD)" and "Progressive Disease (PD)"

4. Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response [1 year]

   Correlating baseline and on treatment levels of additional growth factors measured in nanograms per milliliter that may be co- or counter- regulated with VEGF with response to treatment

5. Concentration of VCAM-1 Reported as a Function of Treatment Response [1 year]

   Correlating baseline and on treatment levels of VCAM-1 measured in micrograms per milliliter that may be co- or counter- regulated with VEGF with response to treatment

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma w/ histologic documentation of the original primary tumor via the pathology report:

• serious, endometrioid, mucinous, or clear cell adenocarcinoma

• undifferentiated, mixed epithelial or transitional cell carcinoma

• Brenner's Tumor

• adenocarcinoma NOS

• Had treatment-free interval following response to bevacizumab (CR, PR, or SD) of < 6 months, or have progressed during treatment w/ a bevacizumab-containing therapy

• Measurable or detectable disease. Measurable is defined by RECIST 1.1. Each lesion must be ≥ 10 mm when measured by CT, 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. Detectable defined as no measurable disease but either ascities/pleural effusion or solid/cystic abnormalities that don't meet RECIST 1.1 - both within the setting of CA125 >2xULN

• Those with measurable disease must have at least one "target lesion" to assess response as defined by RECIST 1.1. Tumors in a previously irradiated field will be designated as "non-target" lesions

• Must have a ECOG Performance Status of 0 or 1

• Free of active infection requiring antibiotics. Exception: uncomplicated UTI

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

• Hormonal therapy directed at the malignant tumor must be d/c at least a week prior to registration. Hormone replacement therapy is permitted

• Other prior therapy directed at malignant tumor, including immunologic agents, must be d/c at least 3 weeks prior to registration; 4 weeks if prior therapy was w/ bevacizumab

• Prior therapy

• must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment.

• Allowed, to receive, but not required to receive, 2 additional cytotoxic regimens for management of recurrent or persistent disease according to the following:

• Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy.

• Patients must NOT have received any non-cytotoxic therapy for management of recurrent or persistent disease other than bevacizumab. Patients are allowed to receive, but are not required to receive, biologic (non-cytotoxic) therapy as part of their primary treatment regimen.

• Must have adequate:

• Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500/mcl, equivalent to (CTCAE v4.0) grade 1. Platelets ≥ 100,000/mcl. Hemoglobin (Hb) ≥ 9.0 g/dL

• Renal function: creatinine ≤ 1.5 x upper limit of normal (ULN)

• Hepatic function: Bilirubin should be w/in normal limits (CTCAE v4.0, grade 1). ALT/AST, should be ≤ 1.5 x ULN (CTCAE v4.0, grade 1). For patients w/ liver metastases, ALT/AST should be ≤ 2.5 x ULN; Alkaline phosphatase should be ≤ 2.5 x ULN (CTCAE v4.0, grade 1)

• Neurologic function: Neuropathy ≤ CTCAE v4.0, grade 1

• Blood coagulation parameters: PT w/ international normalized ratio (INR) < 1.5 x ULN & a PTT < 1.5 x ULN (or an in-range PTT if on a stable dose of therapeutic heparin). Low molecular weight heparin (enoxaparin or alternative anticoagulants (other than warfarin)) are acceptable.

• Signed informed consent & authorization permitting release of personal health information

• Negative serum pregnancy test if of childbearing potential prior to study entry & use of effective form of contraception until 3 months after receiving last drug treatment

• Patients may have undergone a major or minor surgical procedure as long as:

• 28 days prior to the first date of study therapy

• Core biopsy or IV Port placement greater than 7 days prior to the first date of study therapy

Exclusion Criteria:

• Previous treatment w/ BIBF 1120.

• Pregnant or breastfeeding.

• Received radiation to more than 25% of marrow-bearing areas

• History of other invasive malignancies, w/ the exception of non-melanoma skin cancer, if there is any evidence of other malignancy being present w/in the last five years.

• Received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for treatment of ovarian, fallopian tube, or primary peritoneal cancer w/in the last 5 years.

• Prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer or localized breast cancer w/in the last 5 years.

• A history of abdominal or tracheal-esophageal fistula, or gastrointestinal perforation

• A history of intra-abdominal abcess w/in 6 months of enrollment

• Serious, uncontrolled, concomitant disorder(s) such as diabetes mellitus

• Patients w/ clinically significant cardiovascular disease including: uncontrolled hypertension: systolic > 150 mm Hg/diastolic > 90 mm Hg; unstable angina or who have had a myocardial infarction w/in the past six months prior to registration; congestive heart failure; cardiac arrhythmia requiring medication (doesn't include asymptomatic atrial fibrillation); grade 2 or greater peripheral vascular disease (at least brief (<24 hours) episodes of ischemia managed non-surgically & w/o permanent deficit.

• Serious non-healing wound, ulcer, or bone factor.

o Granulating incisions healing by secondary intention w/ no evidence of fascial dehiscence or infection ARE eligible but require weekly wound examinations.

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

• History/evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled w/ standard medical therapy, any brain metastases, CVA, TIA, or subarachnoid hemorrhage w/in 6 months of the first date of treatment on this study.

• Central pulmonary metastases/recent hemoptysis (≥1/2 tsp of red blood) w/in 28 days of registration.

• Clinically significant proteinuria (i.e. >Grade 1) or UPC ratio above 1.0

• Suspicion of transmural tumor bowel involvement based on the investigator's discretion.

• Clinical symptoms/signs of gastrointestinal obstruction & require IV hydration &/or nutrition.

• Patients taking warfarin are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Cancer Institute	Durham	North Carolina	United States	27710
2	University of Virginia	Charlottesville	Virginia	United States	22908
3	Virginia Oncology Associates	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• AA Secord
• Boehringer Ingelheim

Investigators

• Principal Investigator: Angeles A Secord, MD, Duke University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 16, 2018

More Information

Publications

None provided.

• Responsible Party: AA Secord, Associate Professor, Duke University
• ClinicalTrials.gov Identifier: NCT01669798
• Other Study ID Numbers: Pro00033060
• First Posted: Aug 21, 2012
• Last Update Posted: Oct 16, 2018
• Last Verified: Oct 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by AA Secord, Associate Professor, Duke University: Recurrent epithelial ovarian carcinoma; Persistent epithelial ovarian carcinoma; Bevacizumab resistant epithelial ovarian carcinoma
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Nintedanib

Study Results

Participant Flow

Recruitment Details	Patients were enrolled from February of 2013 to July of 2017 at three cancer clinics in North Carolina and Virginia.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Period Title: Overall Study
STARTED	32
COMPLETED	27
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Overall Participants	27
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 51.9%
>=65 years	13 48.1%
Sex: Female, Male (Count of Participants)
Female	27 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	25 92.6%
Unknown or Not Reported	2 7.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 7.4%
White	24 88.9%
More than one race	0 0%
Unknown or Not Reported	1 3.7%
Primary site of tumor (Count of Participants)
Ovary	26 96.3%
Peritoneum	1 3.7%
Histologic tumor type (Count of Participants)
Adenocarcinoma, Unspecified	1 3.7%
Clear Cell Carcinoma	1 3.7%
Other: Poorly Differentiated Adenocarcinoma	1 3.7%
Serous Adenocarcinoma	24 88.9%
Platinum based treatment resistant/sensitive (Count of Participants)
Platinum Resistant	22 81.5%
Platinum Sensitive	5 18.5%
Antecedent Bevacizumab (bev) therapy prior to starting trial (Count of Participants)
Front-line chemo with bev, plus bev maintenance	9 33.3%
Front-line chemo with bev, without bev maintenance	2 7.4%
Second-line chemo with bev, plus bev maintenance	5 18.5%
Secon-line chemo with bev, without bev maintenance	4 14.8%
Second line single agent bevacizumab	6 22.2%
Third-line chemotherapy plus bevacizumab	1 3.7%
Number of prior therapy regimens (Count of Participants)
One prior regimen	8 29.6%
Two prior regimens	10 37%
Three prior regimens	7 25.9%
Four prior regimens	2 7.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Who Survive Progression-free
Description	Measure of Progression Free Survival (PFS) by the percentage of patients who survive progression-free for at least 6 months after initiating study therapy in patients with bevacizumab-resistant, persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The analysis was to be based on 27 evaluable patients for the first stage. Subjects were considered evaluable if they completed at least one cycle of study drug. Of the 27 subjects, one was not considered evaluable because they did not receive a full cycle.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	26
Number (95% Confidence Interval) [percentage of participants]	11.5 42.6%

2. Secondary Outcome

Title	Objective Tumor Response Via RECIST (Response Evaluation Criteria in Solid Tumors) 1.1
Description	Evaluating the percentage of patients who have objective tumor response (complete or partial) based on RECIST 1.1 criteria.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Responders are those who achieved a partial response (PR). No subjects achieved a complete response (CR).

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	27
Number (95% Confidence Interval) [percentage of participants]	7.4 27.4%

3. Secondary Outcome

Title	Duration of Progression-Free Survival
Description	The duration of progression-free survival and overall survival measured in months; Progression-Free Survival (PFS) is defined as the duration of time from study entry to time of progression or death, whichever occurs first.
Time Frame	Through study completion, on average 2 years

Outcome Measure Data

Analysis Population Description

Analysis stratified results between PFS (Progression Free Survival) and OS (Overall Survival). Confidence interval and results based on Kaplan Meier Estimates.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	27
Progression Free Survival (PFS)	1.8
Overall Survival (OS)	16

4. Secondary Outcome

Title	Objective Tumor Response Based on GCIG CA-125 Criteria
Description	The proportion of patients who have objective tumor response (complete or partial) based on Gynaecologic Cancer InterGroup(GCIG) CA-125 criteria which is: "A response according to CA 125 has occurred if there is at least a 50% reduction in CA 125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days.".
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Twenty five subjects were analyzed based on the Gynaecologic Cancer Intergroup response CA125 response criteria. Two subjects data were unavailable.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	25
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Adverse Event Frequency and Severity
Description	To determine frequency and severity of adverse events as assessed using NCI Common Toxicity Criteria version 4.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All adverse events considered possible, probably, or definitely related to study drug. Reported regardless of severity.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	27
Anemia	2 7.4%
Sinus tachycardia	1 3.7%
Tinnitus	1 3.7%
Abdominal pain	7 25.9%
Bloating	3 11.1%
Diarrhea	17 63%
Dry mouth	1 3.7%
Constipation	4 14.8%
Dyspepsia	1 3.7%
Gastroesophageal reflux disease	1 3.7%
Nausea	17 63%
Vomiting	13 48.1%
Chills	1 3.7%
Edema limbs	3 11.1%
Fatigue	14 51.9%
Non-cardiac chest pain	1 3.7%
Alanine aminotransferase increased	10 37%
Alkaline phosphatase increased	8 29.6%
Aspartate aminotransferase increased	12 44.4%
Creatinine increased	1 3.7%
Neutrophil count decreased	1 3.7%
Platelet count decreased	2 7.4%
Weight loss	3 11.1%
Anorexia	4 14.8%
Hypoalbuminemia	2 7.4%
Hypocalcemia	1 3.7%
Hypomagnesemia	4 14.8%
Hyponatremia	4 14.8%
Arthralgia	4 14.8%
Arthritis	1 3.7%
Back Pain	2 7.4%
Bone pain	1 3.7%
Pain in extremity	1 3.7%
Dysgeusia	2 7.4%
Headache	8 29.6%
Hematuria	1 3.7%
Proteinuria	4 14.8%
Urinary incontinence	1 3.7%
Vaginal dryness	1 3.7%
Vaginal pain	1 3.7%
Atelectasis	1 3.7%
Dyspnea	2 7.4%
Pleural effusion	1 3.7%
Wheezing	1 3.7%
Rash maculo-papular	1 3.7%
Hypertension	4 14.8%
Intermittent leg cramps	1 3.7%
Bilateral neuropathy, hands and feet	1 3.7%

6. Other Pre-specified Outcome

Title	Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response
Description	Correlating baseline and on treatment levels of additional growth factors measured in picograms per milliliter that may be co- or counter- regulated with VEGF with response to treatment
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Biomarker levels measured and stratified into two groups: those who experienced either Partial Response (PR) or Stable Disease (SD); and those who experienced Progressive Disease (PD). Data was not collected for one subject.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	26
CD73: Partial Response or Stable Disease	3.0
CD73: Progressive Disease	3.8
HGF: Partial Response or Stable Disease	130.1
HGF: Progressive Disease	191.0
IL-6: Partial Response or Stable Disease	18.2
IL-6: Progressive Disease	32.6
PDGF-AA: Partial Response or Stable Disease	89.5
PDGF-AA: Progressive Disease	233.9
PDGF-BB: Partial Response or Stable Disease	184.7
PDGF-BB (pg/ml): PD	396.4
PIGF: Partial Response or Stable Disease	23.4
PIGF: Progressive Disease	24.3
SDF-1: Partial Response or Stable Disease	1968.6
SDF-1: Progressive Disease	2121.9
TGFBeta-R3: Partial Respone or Stable Disease	50.6
TGFBeta-R3: Progressive Disease	52.5
Ang2: Partial Response or Stable Disease	261.1
Ang2: Progressive Disease	189.5
BMP-9: Partial Response or Stable Disease	47.0
BMP-9: Progressive Disease	45.9

7. Other Pre-specified Outcome

Title	Coagulation and Endothelial Cell Activation Markers
Description	To measure baseline and on treatment levels of additional growth factors that may be co- or counter- regulated with VEGF and correlate with response to treatment.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

We initially planned to measure baseline and on treatment levels of coagulation and endothelial cell activation markers that may predict for thrombotic or bleeding risks related to treatment. These markers are best analyzed in citrated plasma and funding was not available for tube collection and analysis.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	0

8. Other Pre-specified Outcome

Title	VEGF Levels Correlated With Treatment Outcome
Description	Baseline levels of VEGF were correlated with treatment outcome. Results are stratified in groups: "Partial Response (PR) or Stable Disease (SD)" and "Progressive Disease (PD)"
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

VEGF levels measured and stratified into two groups: those who experienced either Partial Response (PR) or Stable Disease (SD); and those who experienced Progressive Disease (PD). Data was not collected for one subject

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	26
Partial Response or Stable Disease	1405
Progressive Disease	1033

9. Other Pre-specified Outcome

Title	Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response
Description	Correlating baseline and on treatment levels of additional growth factors measured in nanograms per milliliter that may be co- or counter- regulated with VEGF with response to treatment
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Biomarker levels measured and stratified into two groups: those who experienced either Partial Response (PR) or Stable Disease (SD); and those who experienced Progressive Disease (PD). Data was not collected for one subject.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	26
ICAM-1: Partial Response or Stable Disease	635.1
ICAM-1: Progressive Disease	686.8
OPN: Partial Response or Stable Disease	643.0
OPN: Progressive Disease	923.0
TGF-Beta1: Partial Response or Stable Disease	122.5
TGF-Beta1: Progressive Disease	90.3
TGF-Beta2: Partial Response or Stable Disease	22.0
TGF-Beta2: Progressive Disease	33.4
TIMP-1: Partial Response or Stable Disease	93.5
TIMP-1: Progressive Disease	116.4
TSP-2: Partial Response or Stable Disease	95.1
TSP-2: Progressive Disease	104.9

10. Other Pre-specified Outcome

Title	Concentration of VCAM-1 Reported as a Function of Treatment Response
Description	Correlating baseline and on treatment levels of VCAM-1 measured in micrograms per milliliter that may be co- or counter- regulated with VEGF with response to treatment
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Biomarker levels measured and stratified into two groups: those who experienced either Partial Response (PR) or Stable Disease (SD); and those who experienced Progressive Disease (PD). Data was not collected for one subject.

Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
Measure Participants	26
VCAM-1: Partial Response or Stable Disease	2.2
VCAM-1: Progressive Disease	2.3

Adverse Events

Time Frame	The study period during which all AEs and SAEs are collected began after informed consent is obtained and initiation of study treatment on Cycle 1, Day 1. It ended 30 days following the last administration of study treatment, or if the patient initiated treatment with a new anti-cancer therapy, or study discontinuation/termination; whichever was earlier.
Arm/Group Title	BIBF 1120
Arm/Group Description	BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy. BIBF 1120: PO 200mg BID
All Cause Mortality
	BIBF 1120
	Affected / at Risk (%)	# Events
Total	22/27 (81.5%)
Serious Adverse Events
	BIBF 1120
	Affected / at Risk (%)	# Events
Total	6/27 (22.2%)
Gastrointestinal disorders
Abdominal Pain	1/27 (3.7%)
General disorders
Non-cardiac chest pain	1/27 (3.7%)
Infections and infestations
Kidney Infection	1/27 (3.7%)
Investigations
Aspartate aminotransferase increased	2/27 (7.4%)
Alanine aminotransferase increased	1/27 (3.7%)
Metabolism and nutrition disorders
Hyponatremia	1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	BIBF 1120
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Anemia	5/27 (18.5%)
Leukocytosis	1/27 (3.7%)
Cardiac disorders
Sinus tachycardia	2/27 (7.4%)
Ear and labyrinth disorders
Tinnitus	1/27 (3.7%)
Endocrine disorders
Endocrine disorders - Other, specify	1/27 (3.7%)
Gastrointestinal disorders
Abdominal distension	1/27 (3.7%)
Abdominal pain	9/27 (33.3%)
Ascites	1/27 (3.7%)
Bloating	6/27 (22.2%)
Constipation	10/27 (37%)
Diarrhea	18/27 (66.7%)
Dry mouth	1/27 (3.7%)
Dyspepsia	2/27 (7.4%)
Gastroesophageal reflux disease	2/27 (7.4%)
Nausea	17/27 (63%)
Vomiting	13/27 (48.1%)
General disorders
Chills	1/27 (3.7%)
Edema limbs	5/27 (18.5%)
Fatigue	15/27 (55.6%)
Fever	1/27 (3.7%)
Non-cardiac chest pain	1/27 (3.7%)
Pain	3/27 (11.1%)
Infections and infestations
Infections and infestations - Other, specify	2/27 (7.4%)
Tooth infection	1/27 (3.7%)
Sinusitis	1/27 (3.7%)
Upper respiratory infection	1/27 (3.7%)
Urinary tract infection	2/27 (7.4%)
Investigations
Alanine aminotransferase increased	9/27 (33.3%)
Alkaline phosphatase increased	8/27 (29.6%)
Aspartate aminotransferase increased	9/27 (33.3%)
Creatinine increased	3/27 (11.1%)
Investigations - Other, specify	1/27 (3.7%)
Neutrophil count decreased	2/27 (7.4%)
Platelet count decreased	3/27 (11.1%)
Weight loss	3/27 (11.1%)
White blood cell decreased	1/27 (3.7%)
Metabolism and nutrition disorders
Anorexia	4/27 (14.8%)
Dehydration	1/27 (3.7%)
Hyperglycemia	1/27 (3.7%)
Hyperkalemia	1/27 (3.7%)
Hypoalbuminemia	4/27 (14.8%)
Hypocalcemia	1/27 (3.7%)
Hypokalemia	1/27 (3.7%)
Hypomagnesemia	6/27 (22.2%)
Hyponatremia	5/27 (18.5%)
Musculoskeletal and connective tissue disorders
Aarthralgia	3/27 (11.1%)
Arthritis	1/27 (3.7%)
Back pain	4/27 (14.8%)
Bone pain	1/27 (3.7%)
Chest wall pain	1/27 (3.7%)
Musculoskeletal and connective tissue disorder- Other, specify	3/27 (11.1%)
Myalgia	1/27 (3.7%)
Neck pain	1/27 (3.7%)
Pain in extremity	1/27 (3.7%)
Nervous system disorders
Dizziness	1/27 (3.7%)
Dysgeusia	3/27 (11.1%)
Headache	9/27 (33.3%)
Nervous system disorders - Other, specify	1/27 (3.7%)
Peripheral sensory neuropathy	1/27 (3.7%)
Psychiatric disorders
Anxiety	2/27 (7.4%)
Depression	1/27 (3.7%)
Renal and urinary disorders
Hematuria	2/27 (7.4%)
Proteinuria	4/27 (14.8%)
Renal and urinary disorders - Other, specify	2/27 (7.4%)
Urinary frequency	2/27 (7.4%)
Urinary incontinence	1/27 (3.7%)
Urinary tract obstruction	1/27 (3.7%)
Reproductive system and breast disorders
Vaginal dryness	1/27 (3.7%)
Vaginal pain	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	2/27 (7.4%)
Cough	3/27 (11.1%)
Dyspnea	6/27 (22.2%)
Pleural effusion	3/27 (11.1%)
Pulmonary edema	1/27 (3.7%)
Wheezing	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/27 (3.7%)
Skin ulceration	2/27 (7.4%)
Vascular disorders
Hypertension	7/27 (25.9%)
Hypotension	1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.