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Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

Primary Purpose

Ovarian Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sorafenib
Topotecan
Sponsored by
Daniela Matei, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase I

Phase II

Arm Description

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

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

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD)
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.
Percentage of Participants With Response
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

Secondary Outcome Measures

Progression-free Survival
To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.
Clinical Benefit
To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.
Duration of Stable Disease
To determine duration of stable disease, in months

Full Information

First Posted
September 5, 2007
Last Updated
February 4, 2016
Sponsor
Daniela Matei, MD
Collaborators
Bayer, Hoosier Cancer Research Network
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1. Study Identification

Unique Protocol Identification Number
NCT00526799
Brief Title
Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Study closed to accrual due unfavorable interim analysis
Study Start Date
September 2007 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Daniela Matei, MD
Collaborators
Bayer, Hoosier Cancer Research Network

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase I
Arm Type
Experimental
Arm Description
Topotecan 3.5 mg/m^2 + Sorafenib dose escalation:
Arm Title
Phase II
Arm Type
Experimental
Arm Description
Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily.
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Topotecan
Intervention Description
3.5mg/m2 weekly, 3 weeks on and one week off.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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.
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.
Title
Percentage of Participants With Response
Description
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
Time Frame
Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.
Time Frame
From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Title
Clinical Benefit
Description
To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.
Time Frame
From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Title
Duration of Stable Disease
Description
To determine duration of stable disease, in months
Time Frame
From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniela Matei, M.D.
Organizational Affiliation
Hoosier Oncology Group, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Medical & Surgical Specialists, LLC
City
Galesburg
State/Province
Illinois
ZIP/Postal Code
61401
Country
United States
Facility Name
Oncology Hematology Associates of SW Indiana
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
Facility Name
Fort Wayne Oncology & Hematology, Inc
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
St. Vincent Hospital Cynecologic Oncology
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Arnett Cancer Care
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47904
Country
United States
Facility Name
Medical Consultants, P.C.
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47303
Country
United States
Facility Name
Schwartz Gynecologic Oncology, PLLC
City
Brightwaters
State/Province
New York
ZIP/Postal Code
11718
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18618737
Citation
Matei D, Emerson RE, Schilder J, Menning N, Baldridge LA, Johnson CS, Breen T, McClean J, Stephens D, Whalen C, Sutton G. Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : a Hoosier Oncology Group trial. Cancer. 2008 Aug 15;113(4):723-32. doi: 10.1002/cncr.23605.
Results Reference
background
Links:
URL
http://www.hoosiercancer.org
Description
Hoosier Cancer Research Network Homepage

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Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

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