Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
Conditions
Keywords
Recurrent epithelial ovarian carcinoma, Persistent epithelial ovarian carcinoma, Bevacizumab resistant epithelial ovarian carcinoma
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.
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.
Interventions
DRUGBIBF 1120
PO 200mg BID
Sponsors
Boehringer Ingelheim
AA Secord
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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.. |
| Adverse Event Frequency and Severity | 1 year | To determine frequency and severity of adverse events as assessed using NCI Common Toxicity Criteria version 4. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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) |
| 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled from February of 2013 to July of 2017 at three cancer clinics in North Carolina and Virginia.
Participants by arm
| Arm | Count |
|---|---|
| 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.
BIBF 1120: PO 200mg BID | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 5 |
Baseline characteristics
| Characteristic | BIBF 1120 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Antecedent Bevacizumab (bev) therapy prior to starting trial Front-line chemo with bev, plus bev maintenance | 9 Participants |
| Antecedent Bevacizumab (bev) therapy prior to starting trial Front-line chemo with bev, without bev maintenance | 2 Participants |
| Antecedent Bevacizumab (bev) therapy prior to starting trial Second-line chemo with bev, plus bev maintenance | 5 Participants |
| Antecedent Bevacizumab (bev) therapy prior to starting trial Second line single agent bevacizumab | 6 Participants |
| Antecedent Bevacizumab (bev) therapy prior to starting trial Secon-line chemo with bev, without bev maintenance | 4 Participants |
| Antecedent Bevacizumab (bev) therapy prior to starting trial Third-line chemotherapy plus bevacizumab | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Histologic tumor type Adenocarcinoma, Unspecified | 1 Participants |
| Histologic tumor type Clear Cell Carcinoma | 1 Participants |
| Histologic tumor type Other: Poorly Differentiated Adenocarcinoma | 1 Participants |
| Histologic tumor type Serous Adenocarcinoma | 24 Participants |
| Number of prior therapy regimens Four prior regimens | 2 Participants |
| Number of prior therapy regimens One prior regimen | 8 Participants |
| Number of prior therapy regimens Three prior regimens | 7 Participants |
| Number of prior therapy regimens Two prior regimens | 10 Participants |
| Platinum based treatment resistant/sensitive Platinum Resistant | 22 Participants |
| Platinum based treatment resistant/sensitive Platinum Sensitive | 5 Participants |
| Primary site of tumor Ovary | 26 Participants |
| Primary site of tumor Peritoneum | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 6 / 27 |
Outcome results
Primary
Percentage of Patients Who Survive Progression-free
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| BIBF 1120 | Percentage of Patients Who Survive Progression-free | 11.5 percentage of participants |
Secondary
Adverse Event Frequency and Severity
To determine frequency and severity of adverse events as assessed using NCI Common Toxicity Criteria version 4.
Time frame: 1 year
Population: All adverse events considered possible, probably, or definitely related to study drug. Reported regardless of severity.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BIBF 1120 | Adverse Event Frequency and Severity | Dyspnea | 2 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Proteinuria | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Headache | 8 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Hematuria | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Anemia | 2 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Sinus tachycardia | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Tinnitus | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Abdominal pain | 7 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Bloating | 3 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Diarrhea | 17 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Dry mouth | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Constipation | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Dyspepsia | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Gastroesophageal reflux disease | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Nausea | 17 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Vomiting | 13 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Chills | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Edema limbs | 3 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Fatigue | 14 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Non-cardiac chest pain | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Alanine aminotransferase increased | 10 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Alkaline phosphatase increased | 8 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Aspartate aminotransferase increased | 12 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Creatinine increased | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Neutrophil count decreased | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Platelet count decreased | 2 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Weight loss | 3 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Anorexia | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Hypoalbuminemia | 2 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Hypocalcemia | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Hypomagnesemia | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Hyponatremia | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Arthralgia | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Arthritis | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Back Pain | 2 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Bone pain | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Pain in extremity | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Dysgeusia | 2 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Urinary incontinence | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Vaginal dryness | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Vaginal pain | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Atelectasis | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Pleural effusion | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Wheezing | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Rash maculo-papular | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Hypertension | 4 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Intermittent leg cramps | 1 Participants |
| BIBF 1120 | Adverse Event Frequency and Severity | Bilateral neuropathy, hands and feet | 1 Participants |
Secondary
Duration of Progression-Free Survival
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
Population: Analysis stratified results between PFS (Progression Free Survival) and OS (Overall Survival). Confidence interval and results based on Kaplan Meier Estimates.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBF 1120 | Duration of Progression-Free Survival | Progression Free Survival (PFS) | 1.8 Months |
| BIBF 1120 | Duration of Progression-Free Survival | Overall Survival (OS) | 16 Months |
Secondary
Objective Tumor Response Based on GCIG CA-125 Criteria
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
Population: Twenty five subjects were analyzed based on the Gynaecologic Cancer Intergroup response CA125 response criteria. Two subjects data were unavailable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BIBF 1120 | Objective Tumor Response Based on GCIG CA-125 Criteria | 0 Participants |
Secondary
Objective Tumor Response Via RECIST (Response Evaluation Criteria in Solid Tumors) 1.1
Evaluating the percentage of patients who have objective tumor response (complete or partial) based on RECIST 1.1 criteria.
Time frame: 1 year
Population: Responders are those who achieved a partial response (PR). No subjects achieved a complete response (CR).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBF 1120 | Objective Tumor Response Via RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 | 7.4 percentage of participants |
Other Pre-specified
Coagulation and Endothelial Cell Activation Markers
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
Population: 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.
Other Pre-specified
Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | ICAM-1: Partial Response or Stable Disease | 635.1 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | ICAM-1: Progressive Disease | 686.8 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | OPN: Partial Response or Stable Disease | 643.0 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | OPN: Progressive Disease | 923.0 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TGF-Beta1: Partial Response or Stable Disease | 122.5 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TGF-Beta1: Progressive Disease | 90.3 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TGF-Beta2: Partial Response or Stable Disease | 22.0 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TGF-Beta2: Progressive Disease | 33.4 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TIMP-1: Partial Response or Stable Disease | 93.5 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TIMP-1: Progressive Disease | 116.4 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TSP-2: Partial Response or Stable Disease | 95.1 nanograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response | TSP-2: Progressive Disease | 104.9 nanograms per milliliter |
Other Pre-specified
Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | CD73: Partial Response or Stable Disease | 3.0 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | CD73: Progressive Disease | 3.8 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | HGF: Partial Response or Stable Disease | 130.1 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | HGF: Progressive Disease | 191.0 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | IL-6: Partial Response or Stable Disease | 18.2 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | IL-6: Progressive Disease | 32.6 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | PDGF-AA: Partial Response or Stable Disease | 89.5 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | PDGF-AA: Progressive Disease | 233.9 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | PDGF-BB: Partial Response or Stable Disease | 184.7 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | PDGF-BB (pg/ml): PD | 396.4 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | PIGF: Partial Response or Stable Disease | 23.4 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | PIGF: Progressive Disease | 24.3 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | SDF-1: Partial Response or Stable Disease | 1968.6 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | SDF-1: Progressive Disease | 2121.9 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | TGFBeta-R3: Partial Respone or Stable Disease | 50.6 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | TGFBeta-R3: Progressive Disease | 52.5 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | Ang2: Partial Response or Stable Disease | 261.1 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | Ang2: Progressive Disease | 189.5 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | BMP-9: Partial Response or Stable Disease | 47.0 picograms per milliliter |
| BIBF 1120 | Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response | BMP-9: Progressive Disease | 45.9 picograms per milliliter |
Other Pre-specified
Concentration of VCAM-1 Reported as a Function of Treatment Response
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBF 1120 | Concentration of VCAM-1 Reported as a Function of Treatment Response | VCAM-1: Partial Response or Stable Disease | 2.2 micrograms per milliliter |
| BIBF 1120 | Concentration of VCAM-1 Reported as a Function of Treatment Response | VCAM-1: Progressive Disease | 2.3 micrograms per milliliter |
Other Pre-specified
VEGF Levels Correlated With Treatment Outcome
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBF 1120 | VEGF Levels Correlated With Treatment Outcome | Partial Response or Stable Disease | 1405 picograms per milliliter |
| BIBF 1120 | VEGF Levels Correlated With Treatment Outcome | Progressive Disease | 1033 picograms per milliliter |