Topotecan 3.5 mg/m^2 + Sorafenib dose escalation:

Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily.

Topotecan 3.5 mg/m^2 + Sorafenib assigned dose level:
Sorafenib Dose level -1=200 mg po daily Sorafenib Dose level 1=400 mg po daily Sorafenib Dose level 2=400 mag po bid

Phase I

Phase II

Total

Sex: Female, Male

Race (NIH/OMB)

Region of Enrollment

ECOG: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) from 0-5 that describes a patient's level of functioning where 0=Fully active, able to carry on all pre-disease performance without restriction and 5=Dead

Eastern Cooperative Onocology Group (ECOG) Perfomance Status

Origin of Cancer

Histology

Number of Prior Therapies

Response Evaluation Criteria in Solid Tumors (RECIST):
Measurable disease is defined by the presence of at least one measureable lesion. If the measureable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
Detectable disease is defined as a patient who does not have measureable disease, but has at least one: 1)CA-125 >= 2x ULN w/in 14d prior to registration 2)Ascites and/or pleural effusion attributed to tumor; 3)solid and/or cystic abnormalities on radiographic imaging that don't meet RECIST definitions for target lesions.

Response Evaluation

Platinum Sensitivity

CA125 at Enrollment

An initial 3 patients will be enrolled at dose level 1. If all 3 patients in dose level 1 complete the first cycle of therapy without a dose limiting toxicity (DLT), 3 patients will be enrolled at dose level 2. If 0 of 3 or 1 of 6 patients in dose level 2 experience a DLT, all subsequent patients will be enrolled in the Phase II cohort at dose level 2. If 2 of the first 3 or 2 of the total 6 patients experience DLT at dose level 2, then dose level 1 will be considered the MTD and used in the second phase.

Phase I Participants

Maximum Tolerated Dose (MTD)

To assess response in patients with recurrent or resistant epithelial ovarian cancer treated with Sorafenib plus Topotecan. Reponse evaluated per RECIST criteria where:
Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Percentage of Participants With Response

To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.

Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily during phase II.
During phase I:
Topotecan 3.5 mg/m^2 + Sorafenib assigned dose level:
Sorafenib Dose level -1=200 mg po daily Sorafenib Dose level 1=400 mg po daily Sorafenib Dose level 2=400 mag po bid

Phase I & II

Progression-free Survival

To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.

Clinical Benefit

To determine duration of stable disease, in months

Duration of Stable Disease

Overall Study

Principal Investigator

Phase I/Phase II

Ovarian Cancer

Phase I: Dose Escalation, Phase II: MTD
Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Sorafenib

3.5mg/m2 weekly, 3 weeks on and one week off.

Topotecan

Medical & Surgical Specialists, LLC

Oncology Hematology Associates of SW Indiana

Fort Wayne Oncology & Hematology, Inc

Indiana University Simon Cancer Center

St. Vincent Hospital Cynecologic Oncology

Arnett Cancer Care

Medical Consultants, P.C.

Schwartz Gynecologic Oncology, PLLC

Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

A Phase I/II Study of Sorafenib in Combination With Topotecan for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer or Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN06-111

Daniela Matei, MD

Sponsor-Investigator

Bayer

Hoosier Cancer Research Network

Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept.

Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept.

Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks

Aflibercept 2.0 mg/kg

Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks

Aflibercept 4.0 mg/kg

Age, Customized

Race/Ethnicity, Customized

OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference.
Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.

Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort

CBR was defined as having a Stable disease (SD) for >= 6 months or a confirmed OR (PR or CR). Based on RECIST:
SD was neither a sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), the persistence of non-target lesions or the maintenance of tumor marker level above the normal limits (for non-target lesions)
CR was the disappearance of all target or non-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD.

Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC

DR was defined as the time interval from the first documentation of CR or PR to the date of tumor progression (or disease progression) as determined by RECIST, or death from any cause, whichever was earlier.
Based on RECIST, progressive disease was at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, the appearance of one or more new target or non-target lesions, or the unequivocal progression of existing non-target lesions.

Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)

TMRR was the proportion of evaluable participants achieving a cancer antigen -125 (CA-125) response based on GCIG definition. A response to CA-125 occurred if after two elevated levels before therapy there was at least a 50% decrease in a post-treatment serum sample, which was confirmed by an independent sample collected 21 days or later that was =< 110% of the post-treatment serum sample.

Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition

TTP was defined as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST. TTP was estimated from Kaplan-Meier curves.
For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC

TTMP was the time interval from the date of randomization to the date of tumor marker progression as was defined by GCIG for the evaluable participants. TTMP was estimated using Kaplan-Meier curves.
For a participant who did not reach tumor marker progression (TMP) during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

Time to Tumor Marker (CA-125) Progression (TTMP)

PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier.
The number of participants with tumor/disease progression are reported. Participants who did not reach tumor progression during study, or had no valid post-baseline tumor burden assessment due to early termination, were censored in the PFS analysis.

Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.

PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. PFS was estimated using Kaplan-Meier curves.
For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

Progression-free Survival (PFS) Time Based on Analysis by the IRC

OS was the time interval between randomization and the date of death from any cause. OS was estimated using Kaplan-Meier curves
A participant was censored for the OS analysis if the participant were alive during the study. The censoring date was either at the date that the participant was last known to be alive or the date of study cut-off, whichever was earlier.

Overall Survival (OS) Time

Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population

All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 30 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.

Overall Safety - Number of Participants With Adverse Events (AE)

The FACT-O questionnaire consists of 38 scored questions (scored from 0-4) that address physical well-being, social/family well-being, emotional well-being, functional well-being and some additional concerns which relate specifically to ovarian cancer symptoms. For each question, higher scores reflect a better quality of life. The total FACT-O score ranges from 0-152, with 152 indicating the best outcome.

Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire

Trial Transparency Team

Neoplasms

Cancer of the Ovary

Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Sanofi-Aventis Administrative Office

Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer

A Multicenter, Randomized, Double-blind, Parallel-arm, Two-stage Study of the Efficacy and Safety of AVE0005 (VEGF Trap) Administered Intravenously Every 2 Weeks in Patients With Platinum-resistant and topotecan-and/or Liposomal Doxorubicin-resistant Advanced Ovarian Cancer

topotecan/инфаркт

Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer

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