Ovarian CancerPhase 2NCT01824615
Sunitinib® in Patients With Recurrent Ovarian Clear Cell Carcinoma
A Phase 2 study testing Sunitinib in people with Ovarian Cancer and Adverse Effects, run by Cathay General Hospital at 1 site in Taiwan.
Trial summary
Patients with early and advanced stages of epithelial ovarian cancer are treated with postoperative systemic chemotherapy after appropriate surgical staging and cytoreductive surgery. For ovarian cancer patients with recurrence, salvage chemotherapy with or without secondary cytoreductive surgery are recommended. Read more about this study
- Who is it for?
- Ages 20 to 80 years, women only
- Conditions the study is for
- Ovarian Cancer, Adverse Effects
- What is being tested?
- Sunitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2013to Jan 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 20 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically (Primary tumor with ≥ 50% clear cell histomorphology) or cytologically confirmed ovarian clear cell carcinoma The disease should be documented recurrence or resistant to primary platinum and paclitaxel based adjuvant chemotherapy.
- Patients are relapsed, not amenable to curative surgery or radiotherapy.
- not considered to required palliative chemotherapy nor radiotherapy
- Abnormal elevated serum CA125 tumor marker for no measurable disease by physical examination or image study, roentgenogram or computed tomography (CT) scan. Serum level of CA125 is higher than 80 IU/ml, or serum level of CA125 is at least 2 fold on day 14 than original serum level of CA125 which is higher than 35 IU/ml but less than 80 IU/ml on day 0.
- Evidence of measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
- Female, 20 years of age or older.
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- GOG performance status of 0 - 2.
- GOG performance status 0-2
- Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgery to NCI CTCAE grade ≤1(except for alopecia).
- Life expectancy of at least 8 weeks
- Adequate organ function as defined by the following criteria:
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN) or AST and ALT ≤5 x ULN if liver function abnormalities are due to underlying malignancy (liver metastases)
- Total serum bilirubin ≤1.5 x ULN
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100,000/µL
- Hemoglobin ≥9.0 g/dL
- Serum creatinine ≤1.5 x ULN
- QTc interval ≤450 msec for males and ≤470 msec for females (based on a mean value from 3 ECGs)
- Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by multigated acquisition (MUGA) scan or echocardiogram
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Any of the following: known, severe hypersensitivity to sunitinib or any of the excipient of this product, unable to swallow sunitinib, previous treatment with sunitinib
- Major surgery or radiation therapy within 4 weeks of study treatment.
- Evidence of tumor bleeding within 4 weeks of study treatment.
- NCI CTCAE grade ≥3 hemorrhage within 4 weeks of study treatment.
- Newly diagnosed CNS metastases that have not been adequately controlled
- Ongoing cardiac dysrhythmias of grade ≥2.
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- Hypertension that cannot be controlled by medication (>150/100 mmHg despite optimal medical therapy).
- Any of the following within the 12 months prior to study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolism.
- Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated with no evidence of recurrent disease for 12 months.
- Ongoing treatment with therapeutic doses (with therapeutic INR levels) of coumarin derivatives (low dose up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed) or oral anti-vitamin K agents.
- PT >1.5 x ULN
- Known human immunodeficiency virus (HIV) infection.
- Current treatment on another clinical trial.
- Pregnancy or breastfeeding. Patients who are unwilling or unable to use adequate contraception to prevent pregnancy during the study. All female patients with reproductive potential must have a negative pregnancy test prior to study entry.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Efficacy of Sunitinib® in Patients With Recurrent Ovarian Clear Cell Carcinoma
Patients with early and advanced stages of epithelial ovarian cancer are treated with postoperative systemic chemotherapy after appropriate surgical staging and cytoreductive surgery. For ovarian cancer patients with recurrence, salvage chemotherapy with or without secondary cytoreductive surgery are recommended. The recommendation for specific primary adjuvant or salvage chemotherapy is cyclophosphamide or paclitaxel plus platinum regimens. Despite the high objective response rate associated with primary chemotherapy in ovarian cancer, the majority of patients will eventually experience disease recurrence and be potential candidates for a second-line treatment approach.
Ovarian clear cell adenocarcinoma (OCCA) is recognized as a distinct histological type of cancer in the WHO-classification of ovarian tumors. OCCA is thought to arise from endometriosis and most patients present with the disease at early stages (International Federation of Gynecology and Obstetrics (FIGO) stages I and II). The incidence of OCCA among epithelial ovarian cancers is estimated to be less than 5-10%. However, OCCA occurs more frequent in Japan and Taiwan (around 10-15%). Unfortunately, OCCA is usually more resistant to systemic chemotherapy than other types and has a poorer prognosis.
Read more
Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of tumor cell growth, angiogenesis, and metastasis. Due to its multi-targeted profile, the pharmacological activity of sunitinib is likely mediated by inhibition of multiple RTK targets and multiple pathways. c-KIT has been implicated in mastocytosis/mast cell leukemia, germ cell cancers, small-cell lung cancer, GISTs, AML, neuroblastoma, melanoma, and ovarian and breast carcinoma. In addition, sunitinib has demonstrated a higher response rate than that reported for anti- VEGF antibody treatment in patients with renal cell carcinoma (RCC). A few clinical case reports indicated sunitinib is effective in treating recurrent ovarian clear cell adenocarcinoma (OCCA) which is almost resistant to second line chemotherapy.
So we would like to conduct this Phase II Sunitinib clinical trial in recurrent / persistent ovarian clear cell cancer patients.
Read the detailed description
Ovarian cancer is the 10th leading cancer in women in Taiwan. There were 894 new cases in 2004 and 297 women died of ovarian cancer in 2001 according to the data released by the Department of Health. The incidence of epithelial ovarian cancer increases with age and the median age at the time of diagnosis is 63 years, and 70% of patients present with advanced disease.
Primary treatment for ovarian cancer consists of appropriate surgical staging and cytoreductive surgery, followed in most patients by systemic chemotherapy. Initial surgery should be a comprehensive staging laparotomy. For patients with clinical stage III or IV disease, the usual recommendation continues to be maximally cytoreductive surgery followed by adjuvant chemotherapy.
Most patients with epithelial ovarian cancer will receive postoperative systemic chemotherapy. Observation is recommended for stage Ia, grade 1 tumors, owing to their high cure rate. For patients with higher-grade and/or higher-stage tumors, systemic chemotherapy is indicated. The recommendation for specific primary chemotherapy/primary adjuvant therapy is Paclitaxel plus platinum regimens. Paclitaxel plus cisplatin or carboplatin are the recommended regimens. The extent of treatment varies with stage of disease. For patients with advanced-stage disease, six cycles of chemotherapy are recommended, whereas for earlier-stage disease, three to six cycles are recommended, pending the results of ongoing studies in this group of patients.
Treatment of relapsed ovarian cancer Despite the high objective response rate associated with primary platinum/taxane-based chemotherapy in advanced ovarian cancer, the majority of patients will eventually experience disease recurrence and be potential candidates for a second-line treatment approach. Treatment options for relapsed cancer are numerous. Patients with platinum-sensitive tumors (response to initial platinum therapy with no relapse for at least 6 months) may be retreated with platinum agents and/or taxanes upon relapse.
Clear cell carcinomas of the ovary comprise approximately 5% of all ovarian neoplasms and exhibit unique features including a more aggressive clinical course and more malignant behavior. Clinically, clear cell carcinomas often present as a large pelvic mass, the majority of which are detected at an early stage (FIGO stage I). Despite the early stage diagnosis, survival rates are significantly lower for women with clear cell carcinoma relative to stage-matched serous adenocarcinoma of the ovary. Furthermore, tumors are more chemoresistant, resulting in a high degree of recurrence and exhibit more frequent early metastasis to lymph nodes and parenchymal organs.
Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of tumor cell growth, angiogenesis, and metastasis. Specifically, sunitinib is a potent ATP-competitive inhibitor of the catalytic activity of a group of closely related RTKs consisting of VEGFR-1, -2, and -3, PDGFR-α and -β, KIT, CSF-1R, FLT-3, and RET. Due to its multi-targeted profile, the pharmacological activity of sunitinib is likely mediated by inhibition of multiple RTK targets and multiple pathways.
In this study, we would like to evaluated the effect of Sunitinib in recurrent / persisted ovarian clear cell carcinoma.
- Conditions
- Ovarian Cancer, Adverse Effects
- Being tested
- Sunitinib
- Keywords
- Sunitinib, recurrent ovarian cancer, clear cell carcinoma
- Medical subject headings
- Ovarian Neoplasms, Adenocarcinoma, Clear Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent
37.5mg everyday from D1-D28
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | Use Sutent for treatment of recurrent / persisted OCCA Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
The tumor response will be assessed according to World Health Organization (WHO) response criteria or Rustin's criteria:
Complete response (CR) Complete disappearance of all clinically detectable lesions for a minimum of 4 weeks. Clinical condition and performance status remains stable or improve.
Partial response (PR) 50% or more decrease in the sum of the products of perpendicular diameters of all measurable lesions or tumor marker-CA125 for a minimum of 4 weeks. Clinical condition and performance status remains stable or improve.
Stable disease (SD) A decrease of less than 50% or an increase of less than 25% of the sum of the products of perpendicular diameters of all measurable lesions or tumor marker CA125 with no development of new lesions for at least 4 weeks.
Progressive disease (PD) Occurrence of new lesions; an increase of 25% or more in the sum of the areas of original measurement, or an elevated 25% of tumor marker CA125.
Measured: 4 weeks after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2013 (estimated)
- Study startJan 2013
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cathay General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chih-Ming Ho, Ph.D., Principal investigator, Cathay General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01824615
- Sponsor's protocol ID
- CT99076
- Other IDs
- TGOG-101
- Status last verified
- Dec 2017
- First submitted
- 19 Mar 2013
- Last updated
- 18 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy of Sunitinib® in Patients With Recurrent Ovarian Clear Cell Carcinoma
- ClinicalTrials.gov ID
- NCT01824615
- Acronym / sponsor ID
- CT99076
- Conditions
- Ovarian Cancer, Adverse Effects
- Keywords
- Sunitinib, recurrent ovarian cancer, clear cell carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Cathay General HospitalUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 5 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with early and advanced stages of epithelial ovarian cancer are treated with postoperative systemic chemotherapy after appropriate surgical staging and cytoreductive surgery. For ovarian cancer patients with recurrence, salvage chemotherapy with or without secondary cytoreductive surgery are recommended. The recommendation for specific primary adjuvant or salvage chemotherapy is cyclophosphamide or paclitaxel plus platinum regimens. Despite the high objective response rate associated with primary chemotherapy in ovarian cancer, the majority of patients will eventually experience disease recurrence and be potential candidates for a second-line treatment approach.
Ovarian clear cell adenocarcinoma (OCCA) is recognized as a distinct histological type of cancer in the WHO-classification of ovarian tumors. OCCA is thought to arise from endometriosis and most patients present with the disease at early stages (International Federation of Gynecology and Obstetrics (FIGO) stages I and II). The incidence of OCCA among epithelial ovarian cancers is estimated to be less than 5-10%. However, OCCA occurs more frequent in Japan and Taiwan (around 10-15%). Unfortunately, OCCA is usually more resistant to systemic chemotherapy than other types and has a poorer prognosis.
Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of tumor cell growth, angiogenesis, and metastasis. Due to its multi-targeted profile, the pharmacological activity of sunitinib is likely mediated by inhibition of multiple RTK targets and multiple pathways. c-KIT has been implicated in mastocytosis/mast cell leukemia, germ cell cancers, small-cell lung cancer, GISTs, AML, neuroblastoma, melanoma, and ovarian and breast carcinoma. In addition, sunitinib has demonstrated a higher response rate than that reported for anti- VEGF antibody treatment in patients with renal cell carcinoma (RCC). A few clinical case reports indicated sunitinib is effective in treating recurrent ovarian clear cell adenocarcinoma (OCCA) which is almost resistant to second line chemotherapy.
So we would like to conduct this Phase II Sunitinib clinical trial in recurrent / persistent ovarian clear cell cancer patients.
Detailed description
Ovarian cancer is the 10th leading cancer in women in Taiwan. There were 894 new cases in 2004 and 297 women died of ovarian cancer in 2001 according to the data released by the Department of Health. The incidence of epithelial ovarian cancer increases with age and the median age at the time of diagnosis is 63 years, and 70% of patients present with advanced disease.
Primary treatment for ovarian cancer consists of appropriate surgical staging and cytoreductive surgery, followed in most patients by systemic chemotherapy. Initial surgery should be a comprehensive staging laparotomy. For patients with clinical stage III or IV disease, the usual recommendation continues to be maximally cytoreductive surgery followed by adjuvant chemotherapy.
Most patients with epithelial ovarian cancer will receive postoperative systemic chemotherapy. Observation is recommended for stage Ia, grade 1 tumors, owing to their high cure rate. For patients with higher-grade and/or higher-stage tumors, systemic chemotherapy is indicated. The recommendation for specific primary chemotherapy/primary adjuvant therapy is Paclitaxel plus platinum regimens. Paclitaxel plus cisplatin or carboplatin are the recommended regimens. The extent of treatment varies with stage of disease. For patients with advanced-stage disease, six cycles of chemotherapy are recommended, whereas for earlier-stage disease, three to six cycles are recommended, pending the results of ongoing studies in this group of patients.
Treatment of relapsed ovarian cancer Despite the high objective response rate associated with primary platinum/taxane-based chemotherapy in advanced ovarian cancer, the majority of patients will eventually experience disease recurrence and be potential candidates for a second-line treatment approach. Treatment options for relapsed cancer are numerous. Patients with platinum-sensitive tumors (response to initial platinum therapy with no relapse for at least 6 months) may be retreated with platinum agents and/or taxanes upon relapse.
Clear cell carcinomas of the ovary comprise approximately 5% of all ovarian neoplasms and exhibit unique features including a more aggressive clinical course and more malignant behavior. Clinically, clear cell carcinomas often present as a large pelvic mass, the majority of which are detected at an early stage (FIGO stage I). Despite the early stage diagnosis, survival rates are significantly lower for women with clear cell carcinoma relative to stage-matched serous adenocarcinoma of the ovary. Furthermore, tumors are more chemoresistant, resulting in a high degree of recurrence and exhibit more frequent early metastasis to lymph nodes and parenchymal organs.
Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of tumor cell growth, angiogenesis, and metastasis. Specifically, sunitinib is a potent ATP-competitive inhibitor of the catalytic activity of a group of closely related RTKs consisting of VEGFR-1, -2, and -3, PDGFR-α and -β, KIT, CSF-1R, FLT-3, and RET. Due to its multi-targeted profile, the pharmacological activity of sunitinib is likely mediated by inhibition of multiple RTK targets and multiple pathways.
In this study, we would like to evaluated the effect of Sunitinib in recurrent / persisted ovarian clear cell carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: SunitinibUse Sutent for treatment of recurrent / persisted OCCA |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically (Primary tumor with ≥ 50% clear cell histomorphology) or cytologically confirmed ovarian clear cell carcinoma The disease should be documented recurrence or resistant to primary platinum and paclitaxel based adjuvant chemotherapy.
- Evidence of measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
- Female, 20 years of age or older.
- GOG performance status of 0 - 2.
- Adequate organ function as defined by the following criteria:
Key exclusion criteria (14 listed)
- Any of the following: known, severe hypersensitivity to sunitinib or any of the excipient of this product, unable to swallow sunitinib, previous treatment with sunitinib
- Major surgery or radiation therapy within 4 weeks of study treatment.
- Evidence of tumor bleeding within 4 weeks of study treatment.
- NCI CTCAE grade ≥3 hemorrhage within 4 weeks of study treatment.
- Newly diagnosed CNS metastases that have not been adequately controlled
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 |
|---|---|---|
| SunitinibAlso: Sutent37.5mg everyday from D1-D28 | Drug | Sunitinib |
Primary outcome
Response rate
Time frame: 4 weeks after completion of treatment
The tumor response will be assessed according to World Health Organization (WHO) response criteria or Rustin's criteria: Complete response (CR) Complete disappearance of all clinically detectable lesions for a minimum of 4 weeks. Clinical condition and performance status remains stable or improve. Partial response (PR) 50% or more decrease in the sum of the products of perpendicular diameters of all measurable lesions or tumor marker-CA125 for a minimum of 4 weeks. Clinical condition and performance status remains stable or improve. Stable disease (SD) A decrease of less than 50% or an increase of less than 25% of the sum of the products of perpendicular diameters of all measurable lesions or tumor marker CA125 with no development of new lesions for at least 4 weeks. Progressive disease (PD) Occurrence of new lesions; an increase of 25% or more in the sum of the areas of original measurement, or an elevated 25% of tumor marker CA125.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
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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.
Chih-Ming Ho, Ph.D. principal investigator
Cathay General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunitinib in people with Ovarian Cancer and Adverse Effects, run by Cathay General Hospital at 1 site in Taiwan.
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 21 inclusion and 14 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: finished, as of the sponsor's last update on 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Response rate (time frame: 4 weeks after completion of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jul 2018.