Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

February 4, 2016 updated by: Daniela Matei, MD

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

This multi-institutional phase I/II clinical trial will test the tolerability and efficacy of the combination sorafenib and topotecan in patients with recurrent ovarian cancer, which is platinum-resistant (recurrence within 6 months from completing platinum based therapy) or refractory (progressive disease during platinum based therapy).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OUTLINE: This is a multi-center study.

  • Topotecan: 4mg/m2 weekly, 3 weeks on and one week off.
  • Sorafenib: Assigned cohort dose for phase I (up to 12 patients) Maximum tolerated dose for phase II (21 total patients)

Cycles will consist of 4 weeks (28 days) with disease evaluations every 8 weeks.

Non-PD and acceptable toxicity: Patients will continue protocol therapy PD or unacceptable toxicity: Patients will discontinue protocol therapy

ECOG performance status 0-1

Life expectancy: Three (3) months

Hematopoietic:

  • White blood cell count (WBC) > 3 K/mm3
  • Hemoglobin (Hgb) > 9 g/dL
  • Platelets > 100 K/mm3
  • Absolute neutrophil count (ANC) > 1.5 K/mm3
  • INR < 1.5 or a PTT within normal limits. NOTE: Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate.
  • No evidence or history of bleeding diathesis or coagulopathy.

Hepatic:

  • Bilirubin < 1.5 x ULN
  • Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN
  • Alanine aminotransferase (ALT, SGPT) < 2.5 x ULN
  • Alkaline phosphate < 2.5 x ULN

Renal:

  • Creatinine < 1.5 x ULN

Cardiovascular:

  • No history of myocardial infarction or angina pectoris or angina equivalent within 6 months prior to registration for protocol therapy (the patient may not be on anti-anginal or anti-arrhythmic medications), or have uncontrolled hypertension or congestive heart failure > class II NYHA

Pulmonary:

  • No thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months.
  • No pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 28 days prior to registration for protocol therapy.
  • No non-pulmonary hemorrhage/bleeding event > CTCAE Grade 3 within 28 days prior to registration for protocol therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Galesburg, Illinois, United States, 61401
        • Medical & Surgical Specialists, LLC
    • Indiana
      • Evansville, Indiana, United States, 47714
        • Oncology Hematology Associates of SW Indiana
      • Fort Wayne, Indiana, United States, 46815
        • Fort Wayne Oncology & Hematology, Inc
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Simon Cancer Center
      • Indianapolis, Indiana, United States, 46260
        • St. Vincent Hospital Cynecologic Oncology
      • Lafayette, Indiana, United States, 47904
        • Arnett Cancer Care
      • Muncie, Indiana, United States, 47303
        • Medical Consultants, P.C.
    • New York
      • Brightwaters, New York, United States, 11718
        • Schwartz Gynecologic Oncology, PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Have histologically-confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer. Enrollment of patients with clear cell histology is encouraged.
  • Have measurable disease according to RECIST or detectable disease by 1) CA-125 at least twice the ULN within 14 days prior to registration for protocol therapy; 2) Ascites and/or pleural effusion attributed to tumor; 3) solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST definitions for target lesions.
  • Have failed at least one prior platinum based chemotherapeutic regimen.
  • No more than 3 prior treatment regimens for epithelial ovarian cancer.
  • Prior radiation therapy is allowed to < 25% of the bone marrow.
  • Be at least 4 weeks since last anti-cancer treatment, radiation or surgery at the time of registration for protocol therapy.
  • No active cancer in addition to the epithelial ovarian cancer within the last 5 years, with the exception of: superficial skin cancer (basal cell or squamous cell skin carcinoma; carcinoma in situ of the cervix; Stage I endometrial cancer with less than 50% invasion of the myometrium, or other adequately treated Stage I or II cancer in complete remission.
  • Age > 18 years at the time of consent
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation
  • Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

Exclusion Criteria:

  • No known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • No prior treatment with anti-angiogenesis therapy.
  • No active CNS metastases.
  • No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
  • No concurrent combination anti-retroviral therapy for the treatment of immunodeficiency.
  • No clinically significant infections requiring antibiotic treatment.
  • No evidence of bowel obstruction, malabsorption, or other contraindication to oral medication.
  • No serious non-healing wound, ulcer, or bone fracture.
  • No major surgery, open biopsy or significant traumatic injury within 28 days of registration for protocol therapy.
  • No use of St. John's Wort or rifampin (rifampicin) while on protocol therapy.
  • No condition that impairs patient's ability to swallow whole pills.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase I
Topotecan 3.5 mg/m^2 + Sorafenib dose escalation:
Drug: Sorafenib

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

Drug: Topotecan
3.5mg/m2 weekly, 3 weeks on and one week off.
Experimental: Phase II
Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily.
Drug: Sorafenib

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

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: Each participant was treated at their assigned dose level on 28 day cycles until disease progression or unacceptable toxicity. Participants were evaluated for toxicity every two weeks.
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.
Each participant was treated at their assigned dose level on 28 day cycles until disease progression or unacceptable toxicity. Participants were evaluated for toxicity every two weeks.
Percentage of Participants With Response
Time Frame: Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation

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
Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.
From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Clinical Benefit
Time Frame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.
From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Duration of Stable Disease
Time Frame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
To determine duration of stable disease, in months
From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Daniela Matei, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bayer
Hoosier Cancer Research Network

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Daniela Matei, M.D., Hoosier Oncology Group, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 5, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GYN06-111

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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