Ovarian CancerPhase 1/2NCT00526799
Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer
A Phase 1/2 study testing Sorafenib and Topotecan in people with Ovarian Cancer, run by Daniela Matei, MD at 8 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Sorafenib and Topotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 8 sitesUnited States
- Study dates
- Sep 2007to Aug 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Schwartz Gynecologic Oncology, PLLC
Brightwaters, New York, 11718
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, 47714
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, 46815
Medical & Surgical Specialists, LLC
Galesburg, Illinois, 61401
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
St. Vincent Hospital Cynecologic Oncology
Indianapolis, Indiana, 46260
Arnett Cancer Care
Lafayette, Indiana, 47904
Medical Consultants, P.C.
Muncie, Indiana, 47303
About this study
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
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).
Read the 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.
- Conditions
- Ovarian Cancer
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
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
TopotecanDrug
3.5mg/m2 weekly, 3 weeks on and one week off.
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | Topotecan 3.5 mg/m^2 + Sorafenib dose escalation: Receives: Drug: Sorafenib; Drug: Topotecan |
| Phase II | Experimental | Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily. Receives: Drug: Sorafenib; Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
Measured: Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation
Secondary outcomes (3)
Progression-free Survival
To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.
Measured: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Clinical Benefit
To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.
Measured: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Duration of Stable Disease
To determine duration of stable disease, in months
Measured: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionJan 2010
- Study completionAug 2010
Why it stopped: Study closed to accrual due unfavorable interim analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daniela Matei, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Hoosier Cancer Research Network
- Responsible party
- Sponsor-investigator, Daniela Matei, MD, Hoosier Cancer Research Network
- Investigators
- Daniela Matei, M.D., Study chair, Hoosier Oncology Group, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00526799
- Sponsor's protocol ID
- GYN06-111
- Status last verified
- Feb 2016
- First submitted
- 5 Sep 2007
- Last updated
- 3 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 18618737
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00526799
- Acronym / sponsor ID
- GYN06-111
- Conditions
- Ovarian Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study closed to accrual due unfavorable interim analysis
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Daniela Matei, MDUniversity, hospital or other
- Collaborators
- Bayer, Hoosier Cancer Research Network
- Study start
- Sep 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 10 Sep 2007 (estimated)
- Results
- Posted 3 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: Sorafenib, Drug: TopotecanTopotecan 3.5 mg/m^2 + Sorafenib dose escalation: |
| Phase II | Experimental | Drug: Sorafenib, Drug: TopotecanTopotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibPhase 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 | Phase I, Phase II |
| Topotecan3.5mg/m2 weekly, 3 weeks on and one week off. | Drug | Phase I, Phase II |
Primary outcome
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.
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
3 secondary outcomes
Progression-free Survival
Time frame: 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
Duration of Stable Disease
Time frame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18618737Matei 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.
- Hoosier Cancer Research Network HomepageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniela Matei, M.D. study chair
Hoosier Oncology Group, Inc.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sorafenib and Topotecan in people with Ovarian Cancer, run by Daniela Matei, MD at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00526799, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2016.