Ovarian CancerPhase 1/2NCT01600573
Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ)
A Phase 1/2 study testing pazopanib in combination with weekly topotecan in people with Ovarian Cancer, run by JSehouli at 1 site in Germany.
Trial summary
This clinical trial shall clarify the efficacy and safety of pazopanib in combination with weekly topotecan in patients with platinum-resistant or intermediate platinum-sensitive recurrent epithelial ovarian cancer, fallopian and peritoneal carcinoma 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?
- pazopanib in combination with weekly topotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteGermany
- Study dates
- May 2012to Mar 2017
- Phase
- Phase 1/2
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent
- histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer
- platinum resistant (recurrence within 6 months of a platinum-containing regimen) or platinum refractory (progression during platinum treatment) or intermediate platinum-sensitive (recurrence within 12 months after a platinum-based primary therapy) disease
- no more than 2 prior treatment regimens for epithelial ovarian cancer
- Age more than 18 years
- ECOG of 0 or 1
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- adequate organ function
- measurable disease or evaluable disease according to RECIST criteria
- able to swallow and retain oral medication
- life expectancy of at least 12 weeks
- non-childbearing potential or negative serum pregnancy test of women of childbearing potential and agrees to use adequate contraception for 14 days before exposure to investigational product, through the dosing period, and for at least 6 months after the last dose of investigational product. Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
Who cannot join
- prior malignancies; subject who have had another malignancy and have been disease-free for 5 years which effect progression free survival, or subject with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
- clinically significant gastrointestinal abnormalities that might interfere with oral dosing or that may increase the risk for gastrointestinal bleeding
- clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- Grade 3 or 4 diarrhoea
- Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
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- poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]
- Prolongation of corrected QT interval (QTc) >450 milliseconds using Bazett's formula
- History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting; myocardial infarction; unstable angina; symptomatic peripheral vascular disease; coronary artery by-pass graft surgery
- Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
- Macroscopic hematuria
- Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug
- Evidence of active bleeding or bleeding diathesis
- known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or involvement of large pulmonary vessels by tumor
- prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
- Chemotherapy or radiation therapy or tumour embolization within 2 weeks prior to the first dose of study drug
- biological therapy, immunotherapy, hormonal therapy or treatment with an investigational agent within 14 days (for bevacizumab, 60 days) or 5 half-lives, whichever is longer prior to the first dose of study drug
- is unable or unwilling to discontinue predefined prohibited medications listed in the protocol (refer to section 4.2.3) for 14 days or five half-lives of a drug (whichever is longer) prior to first dose of study drug and for the duration of the study
- any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia
- known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
- psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
- clinically assessed as having inadequate venous access for PK sampling
- any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
- legal incapacity or limited legal capacity
- Participation in another clinical study with experimental therapy within the 30 days before start of treatment
- Subjects housed in an institution on official or legal orders
- Pregnancy or lactation period
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Charité Campus Virchow-Klinikum
Berlin, 13353
Jalid Sehouli, Prof. Dr., +49 (0) 30 450 ext. 564002, jalid.sehouli@charite.de
Radoslav Chekerov, Dr., +49 (0) 30/450 ext. 664399, radoslav.chekerov@charite.de
About this study
Official title: A Phase I/II Study of Pazopanib and Weekly Topotecan in Patients With Platinum-resistant or Intermediate-sensitive Recurrent Ovarian Cancer
This clinical trial shall clarify the efficacy and safety of pazopanib in combination with weekly topotecan in patients with platinum-resistant or intermediate platinum-sensitive recurrent epithelial ovarian cancer, fallopian and peritoneal carcinoma
Read the detailed description
This study is a prospective single-arm, open-label, multicenter phase I/II trial. The phase I-trial is a dose-escalation trial to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan. The phase II-trial is a single arm open-label trial to further assess the safety and the efficacy of this combination of treatment.
- Conditions
- Ovarian Cancer
- Being tested
- pazopanib in combination with weekly topotecan
- Keywords
- 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.
pazopanib in combination with weekly topotecanDrug
Also called pazopanib in combination with weekly topotean
- Topotecan as an IV infusion over 30 minutes on days 1, 8, and 15 of a 28 day cycle and
- Pazopanib orally once daily continuous dosing in the following dose levels:
Phase I Trial:
Dose level -I: Topotecan weekly 3mg/m2, Pazopanib 400 mg Dose level I: Topotecan weekly 4mg/m2, Pazopanib 400 mg Dose level II: Topotecan weekly 4mg/m2, Pazopanib 600 mg Dose level III: Topotecan weekly 4mg/m2, Pazopanib 800 mg
Phase II Trial:
Phase II will either use the MTD as determined in Phase I or a lower dose if deemed necessary.
| Study group | Role | What they receive |
|---|---|---|
| pazopanib plus weekly topotecan | Experimental | pazopanib in combination with weekly topotecan Receives: Drug: pazopanib in combination with weekly topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Assessment of dose-limiting toxicity in order to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan
Dose-limiting toxicities are defined as follows:
- grade 3 or 4 non-hematologic toxicity other than nausea or vomiting
- grade 3 or 4 thrombocytopenia (platelet count less than 50000/µl)
- grade 4 neutropenia lasting ≥ 7 days or febrile neutropenia defined as ANC <1000/µl concurrent with fever
- Any grade 2 and more toxicity of cycle 1 other than nausea, vomiting, rash, alopecia or anemia, that persisted over 35 days.
Measured: after 4 weeks
• Phase II: Progression-free survival according to RECIST criteria
- Phase II: Progression-free survival according to RECIST criteria
Measured: up to 3.5 years
Secondary outcomes (8)
• Overall survival
- Overall survival
Measured: up to 3.5 years
• Response rate (CR, PR) according to RECIST criteria
- Response rate (CR, PR) according to RECIST criteria
Measured: up to 3.5 years
• Clinical benefit rate (CR, PR, SD)
- Clinical benefit rate (CR, PR, SD)
Measured: up to 3.5 years
• Duration of response
- Duration of response
Measured: up to 3.5 years
• Time to progression (TTP)
- Time to progression (TTP)
Measured: up to 3.5 years
• Evaluation of CA-125 tumour response
- Evaluation of CA-125 tumour response
Measured: up to 3.5 years
Safety and tolerability of pazopanib in combination with weekly topotecan
Incidence and type of AE in terms of:
- All AE,
- Related AE,
- SAE,
- Related SAE,
- NCI-CTC (version 4.0) grade 3 and 4 AE,
- Related NCI-CTC (version 4.0) grade 3 and 4 AE,
- AE leading to treatment discontinuation,
- Incidence of, and reason for, deaths.
Measured: up to 3.5 years
• Quality of life as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire
- Quality of life as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire
Measured: up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2012 (estimated)
- Study startMay 2012
- Primary completionMar 2017 (estimated)
- Study completionMar 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- JSehouli
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor-investigator, JSehouli, Charite University, Berlin, Germany
- Investigators
- jalid Sehouli, Prof. Dr., Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01600573
- Sponsor's protocol ID
- PazTo_2010
- Status last verified
- Oct 2016
- First submitted
- 9 May 2012
- Last updated
- 11 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Chekerov R, Arndt T, Pietzner K, Canzler U, Wimberger P, Strauss HG, Mahner S, Woelber L, de Gregorio N, Stocker G, von Abel E, Neunhoeffer T, Belau AK, Mustea A, Yalinkaya I, Braicu EI, Richter R, Sehouli J; NOGGO ovarian cancer study group. Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ). J Cancer Res Clin Oncol. 2023 Aug;149(10):7637-7649. doi: 10.1007/s00432-023-04647-9. Epub 2023 Mar 31.
PubMed 37000264
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Pazopanib and Weekly Topotecan in Patients With Platinum-resistant or Intermediate-sensitive Recurrent Ovarian Cancer
- ClinicalTrials.gov ID
- NCT01600573
- Acronym / sponsor ID
- PazTo_2010
- Conditions
- Ovarian Cancer
- Keywords
- ovarian cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- JSehouliUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- May 2012
- Primary completion
- Mar 2017 (estimated)
- Study completion
- Mar 2017 (estimated)
- First posted
- 17 May 2012 (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.
This clinical trial shall clarify the efficacy and safety of pazopanib in combination with weekly topotecan in patients with platinum-resistant or intermediate platinum-sensitive recurrent epithelial ovarian cancer, fallopian and peritoneal carcinoma
Detailed description
This study is a prospective single-arm, open-label, multicenter phase I/II trial. The phase I-trial is a dose-escalation trial to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan. The phase II-trial is a single arm open-label trial to further assess the safety and the efficacy of this combination of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pazopanib plus weekly topotecan | Experimental | Drug: pazopanib in combination with weekly topotecanpazopanib in combination with weekly topotecan |
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)
- written informed consent
- histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer
- platinum resistant (recurrence within 6 months of a platinum-containing regimen) or platinum refractory (progression during platinum treatment) or intermediate platinum-sensitive (recurrence within 12 months after a platinum-based primary therapy) disease
- no more than 2 prior treatment regimens for epithelial ovarian cancer
- Age more than 18 years
Key exclusion criteria (28 listed)
- prior malignancies; subject who have had another malignancy and have been disease-free for 5 years which effect progression free survival, or subject with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
- clinically significant gastrointestinal abnormalities that might interfere with oral dosing or that may increase the risk for gastrointestinal bleeding
- clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- Grade 3 or 4 diarrhoea
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 |
|---|---|---|
| pazopanib in combination with weekly topotecanAlso: pazopanib in combination with weekly topotean* Topotecan as an IV infusion over 30 minutes on days 1, 8, and 15 of a 28 day cycle and * Pazopanib orally once daily continuous dosing in the following dose levels: Phase I Trial: Dose level -I: Topotecan weekly 3mg/m2, Pazopanib 400 mg Dose level I: Topotecan weekly 4mg/m2, Pazopanib 400 mg Dose level II: Topotecan weekly 4mg/m2, Pazopanib 600 mg Dose level III: Topotecan weekly 4mg/m2, Pazopanib 800 mg Phase II Trial: Phase II will either use the MTD as determined in Phase I or a lower dose if deemed necessary. | Drug | pazopanib plus weekly topotecan |
Primary outcome
Phase I: Assessment of dose-limiting toxicity in order to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan
Time frame: after 4 weeks
Dose-limiting toxicities are defined as follows: * grade 3 or 4 non-hematologic toxicity other than nausea or vomiting * grade 3 or 4 thrombocytopenia (platelet count less than 50000/µl) * grade 4 neutropenia lasting ≥ 7 days or febrile neutropenia defined as ANC <1000/µl concurrent with fever * Any grade 2 and more toxicity of cycle 1 other than nausea, vomiting, rash, alopecia or anemia, that persisted over 35 days.
• Phase II: Progression-free survival according to RECIST criteria
Time frame: up to 3.5 years
• Phase II: Progression-free survival according to RECIST criteria
8 secondary outcomes
• Overall survival
Time frame: up to 3.5 years
• Response rate (CR, PR) according to RECIST criteria
Time frame: up to 3.5 years
• Clinical benefit rate (CR, PR, SD)
Time frame: up to 3.5 years
• Duration of response
Time frame: up to 3.5 years
• Time to progression (TTP)
Time frame: up to 3.5 years
• Evaluation of CA-125 tumour response
Time frame: up to 3.5 years
Safety and tolerability of pazopanib in combination with weekly topotecan
Time frame: up to 3.5 years
• Quality of life as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire
Time frame: up to 3.5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2016.
- Derived from this study: PubMed 37000264Chekerov R, Arndt T, Pietzner K, Canzler U, Wimberger P, Strauss HG, Mahner S, Woelber L, de Gregorio N, Stocker G, von Abel E, Neunhoeffer T, Belau AK, Mustea A, Yalinkaya I, Braicu EI, Richter R, Sehouli J; NOGGO ovarian cancer study group. Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ). J Cancer Res Clin Oncol. 2023 Aug;149(10):7637-7649. doi: 10.1007/s00432-023-04647-9. Epub 2023 Mar 31.
- 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.
jalid Sehouli, Prof. Dr. principal investigator
Charite University, Berlin, Germany
1 site 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 pazopanib in combination with weekly topotecan in people with Ovarian Cancer, run by JSehouli at 1 site in Germany.
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 28 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: status not confirmed, as of the sponsor's last update on 11 Oct 2016. 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 Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jalid Sehouli, Prof. Dr. (+49 (0) 30 450 ext. 564002, jalid.sehouli@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Assessment of dose-limiting toxicity in order to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan (time frame: after 4 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 NCT01600573, 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 11 Oct 2016.