Symptoms and General Pathology

All Conditions

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Gland and Hormone Related Diseases

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Fallopian Tube Neoplasms

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Genital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Bevacizumab

Nintedanib

Protein Kinase Inhibitors

Enzyme Inhibitors

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

Angeles A Secord, MD

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.

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.

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

Phase II Evaluation of BIBF 1120 in the Treatment of Bevacizumab-Resistant, Persistent, or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

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

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.

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)"

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

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

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.

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

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.

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.".

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

Boehringer Ingelheim

AA Secord

Associate Professor

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

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Ovary

Peritoneum

Primary site of tumor

Adenocarcinoma, Unspecified

Clear Cell Carcinoma

Other: Poorly Differentiated Adenocarcinoma

Serous Adenocarcinoma

Histologic tumor type

Platinum Resistant

Platinum Sensitive

Platinum based treatment resistant/sensitive

Front-line chemo with bev, plus bev maintenance

Front-line chemo with bev, without bev maintenance

Second-line chemo with bev, plus bev maintenance

Secon-line chemo with bev, without bev maintenance

Second line single agent bevacizumab

Third-line chemotherapy plus bevacizumab

Antecedent Bevacizumab (bev) therapy prior to starting trial

One prior regimen

Two prior regimens

Three prior regimens

Four prior regimens

Number of prior therapy regimens

Angeles Alvarez Secord

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.

Percentage of Patients Who Survive Progression-free

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

Objective Tumor Response Via RECIST (Response Evaluation Criteria in Solid Tumors) 1.1

Progression Free Survival (PFS)

Overall Survival (OS)

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

Duration of Progression-Free Survival

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

Objective Tumor Response Based on GCIG CA-125 Criteria

Anemia

Sinus tachycardia

Tinnitus

Abdominal pain

Bloating

Diarrhea

Dry mouth

Constipation

Dyspepsia

Gastroesophageal reflux disease

Nausea

Vomiting

Chills

Edema limbs

Fatigue

Non-cardiac chest pain

Alanine aminotransferase increased

Alkaline phosphatase increased

Aspartate aminotransferase increased

Creatinine increased

Neutrophil count decreased

Platelet count decreased

Weight loss

Anorexia

Hypoalbuminemia

Hypocalcemia

Hypomagnesemia

Hyponatremia

Arthralgia

Arthritis

Back Pain

Bone pain

Pain in extremity

Dysgeusia

Headache

Hematuria

Proteinuria

Urinary incontinence

Vaginal dryness

Vaginal pain

Atelectasis

Dyspnea

Pleural effusion

Wheezing

Rash maculo-papular

Hypertension

Intermittent leg cramps

Bilateral neuropathy, hands and feet

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

Adverse Event Frequency and Severity

CD73: Partial Response or Stable Disease

CD73: Progressive Disease

HGF: Partial Response or Stable Disease

HGF: Progressive Disease

IL-6: Partial Response or Stable Disease

IL-6: Progressive Disease

PDGF-AA: Partial Response or Stable Disease

PDGF-AA: Progressive Disease

PDGF-BB: Partial Response or Stable Disease

PDGF-BB (pg/ml): PD

PIGF: Partial Response or Stable Disease

PIGF: Progressive Disease

SDF-1: Partial Response or Stable Disease

SDF-1: Progressive Disease

TGFBeta-R3: Partial Respone or Stable Disease

TGFBeta-R3: Progressive Disease

Ang2: Partial Response or Stable Disease

Ang2: Progressive Disease

BMP-9: Partial Response or Stable Disease

BMP-9: Progressive Disease

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.

Concentration of Select Growth Factors Reported Measured in Picograms Per Milliliter as a Function of Treatment Response

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.

Coagulation and Endothelial Cell Activation Markers

Partial Response or Stable Disease

Progressive Disease

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

VEGF Levels Correlated With Treatment Outcome

ICAM-1: Partial Response or Stable Disease

ICAM-1: Progressive Disease

OPN: Partial Response or Stable Disease

OPN: Progressive Disease

TGF-Beta1: Partial Response or Stable Disease

TGF-Beta1: Progressive Disease

TGF-Beta2: Partial Response or Stable Disease

TGF-Beta2: Progressive Disease

TIMP-1: Partial Response or Stable Disease

TIMP-1: Progressive Disease

TSP-2: Partial Response or Stable Disease

TSP-2: Progressive Disease

Concentration of Select Growth Factors Measured in Nanograms Per Milliliter Reported as a Function of Treatment Response

VCAM-1: Partial Response or Stable Disease

VCAM-1: Progressive Disease

Concentration of VCAM-1 Reported as a Function of Treatment Response

Overall Study

Spots Global Cancer Trial Database for bevacizumab resistant epithelial ovarian carcinoma