Epithelial Ovarian CancerPhase 1/2NCT02012192
GANNET53: Ganetespib in Metastatic, p53-mutant, Platinum-resistant Ovarian Cancer
A Phase 1/2 study testing Ganetespib and Paclitaxel in people with Epithelial Ovarian Cancer and Fallopian Tube Cancer, run by Medical University Innsbruck at 10 sites in 4 countries.
Trial summary
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy causing 41900 deaths annually in Europe. The predominance of aggressive Type II tumours, which are characterised by a high frequency of p53 mutations, and primary or acquired resistance to platinum-based chemotherapy profoundly contribute to… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
- What is being tested?
- Ganetespib and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 10 sitesin 4 countries
- Study dates
- 4 Jul 2014to 4 Dec 2017
- 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
- Ability to understand and willingness to sign and date a written informed consent document
- Female patients ≥18 years of age
- High-grade serous, high-grade endometrioid, or undifferentiated epithelial ovarian, fallopian tube or primary peritoneal cancer
- Patients in part II: High-grade serous, high-grade endometrioid, or undifferentiated epithelial ovarian, fallopian tube or primary peritoneal cancer confirmed by central histopathology through archival formalin-fixed paraffin embedded (FFPE) or fresh-frozen tumour samples.
- Platinum-resistant disease:
- primary platinum-resistant disease: progression > 1 month and ≤ 6 months after completion of primary platinum-based therapy
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- secondary platinum-resistant disease (including secondary platinum-refractory disease): progression ≤ 6 months after (or during) reiterative platinum-based therapy
- Patients must have disease that is measurable according to RECIST 1.1 or assessable according to the GCIG (Eastern Cooperative Oncology Group) CA-125 criteria
- ECOG performance status of 0-1
- Life expectancy of at least 3 months as assessed by the investigator
- Adequate function of the bone marrow:
- Platelets ≥100 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Haemoglobin ≥ 8.5 g/dl. Patients may receive blood transfusion(s) to maintain haemoglobin values > 8.5 g/dl.
- Adequate organ functions:
- Creatinine < 2 mg/dl (<177 µmol/L)
- Total bilirubin ≤ 1.5 x upper limit of normal
- SGOT ( serum glutamate oxaloacetate transaminase)/SGPT (serum glutamate pyruvate transaminase) (AST/ALT) ≤ 3 x upper limit of normal
- Urinanalysis or urine dipstick for proteinuria less than 2+. Patients with ≥ 2+ on dipstick should undergo 24-hour urine collection and must demonstrate < 1 g of protein/24 hours. Alternatively, proteinuria testing can be performed according to local standards
- Negative urine/serum pregnancy test in women of childbearing potential (WOCBP, see section 5). WOCBP who are sexually active, agree to use highly effective means of contraception during the study and for at least 6 months post-study treatment. Allowed are accepted and effective non-hormonal methods of contraception and sexual abstinence or vasectomised partners (>3 months previously). Vasectomy has to be confirmed by two negative semen analyses.
- Availability of archival ovarian cancer tissue for central histopathological review and p53 mutational analysis
Who cannot join
- Ovarian tumours with low malignant potential (i.e. borderline tumours)
- Primary platinum-refractory disease (progression during primary platinum-based chemotherapy)
- PRIOR, CURRENT OR PLANNED TREATMENT:
- Previous treatment with > 2 chemotherapy regimens in the platinum-resistant setting (excluding targeted and endocrine therapies).
- More than 4 previous lines of chemotherapy.
- Major surgery within 2 weeks prior to first dose of ganetespib
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- PRIOR OR CONCOMITANT CONDITIONS OR PROCEDURES:
- Patients with a history of prior malignancies, except, disease-free time-frame of ≥ 3 years prior to randomisation.
- Patients with prior in-situ carcinomas, except:
- complete removal of the tumour is given
- Known history of severe (grade 3 or 4) allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol [PEG] 300 and Polysorbate 80)
- History of intolerance or hypersensitivity to paclitaxel and/or adverse events related to paclitaxel that resulted in paclitaxel being permanently discontinued
- Peripheral neuropathy of grade > 2 per NCI CTCAE (Common Toxicity Criteria for Adverse Effects), version 4.03, within 4 weeks prior to randomisation
- Clinical symptomatic bowel obstruction at time of screening
- Left ventricular ejection fraction defined by MUGA (multigated acquisition)/ECHO below the institutional lower limit of normal
- Patients with symptomatic brain metastases
- Significant cardiac disease: New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 month; or uncontrolled atrial or ventricular cardiac arrhythmias.
- History of prolonged QT syndrome, or family member with prolonged QT syndrome
- QTc (corrected QT interval) interval > 470 msec when 3 consecutive EKG values are averaged
- Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted
- Second- or third-degree atrioventricular (AV) block, except:
- treated with a permanent pacemaker
- Complete left bundle branch block (LBBB)
- Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.
- Participation in another clinical study with experimental therapy within 28 days before start of treatment.
- Women who are pregnant or are lactating
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Germany5 sites
Universitätsmedizin Berlin Charité, Dept. for Gynecology
Berlin, 10117
University Hospital Carl Gustav Carus Dresden, Department of Gynaecology and Obstetrics
Dresden, 01069
Kliniken Essen Mitte, Evang. Huyssens-Stiftung / Knappschaft GmbH Department of Gynaecologic Oncology
Essen, 45136
Universitätsklinikum Hamburg-Eppendorf Dept. of Gynecology and Gynecologic Oncology
Hamburg, 20246
Otto-von-Guericke-Universität Magdeburg
Magdeburg, 39106
France3 sites
Centre de lutte contre le cancer Francois Baclesse
Caen, 14076
Centre Anticancereux Léon Bérard
Lyon, 69373
Assistance Publique - Hôpitaux de Paris Medical Oncology Department
Paris, 45004
Austria1 site
Medical University Innsbruck, Department for Gynaecology and Obstetrics
Innsbruck, 6020
Belgium1 site
Katholieke Universiteit Leuven, Dept. of Gynaecologic Oncology
Leuven, 3000
About this study
Official title: A Two-part, Multicentre, International Phase I and II Trial Assessing the Safety and Efficacy of the Hsp90 Inhibitor Ganetespib in Combination With Paclitaxel Weekly in Women With High-grade Serous, High-grade Endometrioid, or Undifferentiated, Platinum-resistant Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy causing 41900 deaths annually in Europe. The predominance of aggressive Type II tumours, which are characterised by a high frequency of p53 mutations, and primary or acquired resistance to platinum-based chemotherapy profoundly contribute to the high mortality rate. With current standard therapy the median overall survival of metastatic platinum-resistant (Pt-R) ovarian cancer patients is only 14 month. There is a pressing need for more effective, innovative treatment strategies to particularly improve survival in this subgroup of EOC patients. This is a drug strategy targeting a central driver of tumour aggressiveness and metastatic ability, namely mutant p53, via an innovative new Hsp90 (heat shock protein 90) inhibition mechanism. The most advanced, second-generation Hsp90 inhibitor will be used, Ganetespib. The first part (Phase I) of the GANNET53 trial will test the safety of Ganetespib in a new combination with standard chemotherapy (Paclitaxel weekly) in Pt-R EOC patients. The second part (randomised Phase II) will examine the efficacy of Ganetespib in combination with standard chemotherapy versus standard chemotherapy alone in EOC patients with Pt-R tumours.
- Being tested
- Ganetespib, Paclitaxel
- Keywords
- High-grade serous, high-grade endometrioid, undifferentiated
- Medical subject headings
- Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Disorders of Sex Development
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanetespibDrug
PaclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| Ganetespib + Paclitaxel | Experimental | Drug: ganetespib, dose will depend on phase I results, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression. Receives: Drug: Ganetespib; Drug: Paclitaxel |
| Paclitaxel | Active comparator | Drug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression Receives: Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
evaluate the efficacy of ganetespib in combination with weekly paclitaxel compared to weekly paclitaxel alone as measured by Progression-free survival (PFS). Response or progression will be evaluated in this study according to Response Evaluation Criteria In Solid Tumors Criteria version 1.1., CA-125 according to published GCIG criteria, and by the investigator on the basis of physical and/or gynaecological examinations.
Measured: Time until progression (median w/o new drug 4 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study start4 Jul 2014
- Primary completion30 Nov 2017
- Study completion4 Dec 2017
Why it stopped: production of IMP has stopped
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.
- Other trials for Epithelial Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Medical University InnsbruckThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University Innsbruck
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission
- Responsible party
- Principal investigator, Nicole Concin, Medical University Innsbruck
- Investigators
- Nicole Concin, MD, Principal investigator, Medical University Innsbruck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012192
- Sponsor's protocol ID
- GANNET53
- Other IDs
- 2013-003868-31
- Status last verified
- Jun 2019
- First submitted
- 2 Dec 2013
- Last updated
- 13 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-part, Multicentre, International Phase I and II Trial Assessing the Safety and Efficacy of the Hsp90 Inhibitor Ganetespib in Combination With Paclitaxel Weekly in Women With High-grade Serous, High-grade Endometrioid, or Undifferentiated, Platinum-resistant Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
- ClinicalTrials.gov ID
- NCT02012192
- Acronym / sponsor ID
- GANNET53
- Keywords
- High-grade serous, high-grade endometrioid, undifferentiated
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: production of IMP has stopped
- Enrolment
- 133 participants (actual)
- Lead sponsor
- Medical University InnsbruckUniversity, hospital or other
- Collaborators
- European Commission
- Study start
- 4 Jul 2014 (actual)
- Primary completion
- 30 Nov 2017 (actual)
- Study completion
- 4 Dec 2017 (actual)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Posted 13 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy causing 41900 deaths annually in Europe. The predominance of aggressive Type II tumours, which are characterised by a high frequency of p53 mutations, and primary or acquired resistance to platinum-based chemotherapy profoundly contribute to the high mortality rate. With current standard therapy the median overall survival of metastatic platinum-resistant (Pt-R) ovarian cancer patients is only 14 month. There is a pressing need for more effective, innovative treatment strategies to particularly improve survival in this subgroup of EOC patients. This is a drug strategy targeting a central driver of tumour aggressiveness and metastatic ability, namely mutant p53, via an innovative new Hsp90 (heat shock protein 90) inhibition mechanism. The most advanced, second-generation Hsp90 inhibitor will be used, Ganetespib. The first part (Phase I) of the GANNET53 trial will test the safety of Ganetespib in a new combination with standard chemotherapy (Paclitaxel weekly) in Pt-R EOC patients. The second part (randomised Phase II) will examine the efficacy of Ganetespib in combination with standard chemotherapy versus standard chemotherapy alone in EOC patients with Pt-R tumours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ganetespib + Paclitaxel | Experimental | Drug: Ganetespib, Drug: PaclitaxelDrug: ganetespib, dose will depend on phase I results, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression. |
| Paclitaxel | Active comparator | Drug: PaclitaxelDrug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Ability to understand and willingness to sign and date a written informed consent document
- Female patients ≥18 years of age
- High-grade serous, high-grade endometrioid, or undifferentiated epithelial ovarian, fallopian tube or primary peritoneal cancer
- Patients in part II: High-grade serous, high-grade endometrioid, or undifferentiated epithelial ovarian, fallopian tube or primary peritoneal cancer confirmed by central histopathology through archival formalin-fixed paraffin embedded (FFPE) or fresh-frozen tumour samples.
- primary platinum-resistant disease: progression > 1 month and ≤ 6 months after completion of primary platinum-based therapy
Key exclusion criteria (26 listed)
- Ovarian tumours with low malignant potential (i.e. borderline tumours)
- Primary platinum-refractory disease (progression during primary platinum-based chemotherapy)
- Previous treatment with > 2 chemotherapy regimens in the platinum-resistant setting (excluding targeted and endocrine therapies).
- More than 4 previous lines of chemotherapy.
- Major surgery within 2 weeks prior to first dose of ganetespib
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 |
|---|---|---|
| Ganetespib | Drug | Ganetespib + Paclitaxel |
| Paclitaxel | Drug | Ganetespib + Paclitaxel, Paclitaxel |
Primary outcome
Progression Free Survival (PFS)
Time frame: Time until progression (median w/o new drug 4 months)
evaluate the efficacy of ganetespib in combination with weekly paclitaxel compared to weekly paclitaxel alone as measured by Progression-free survival (PFS). Response or progression will be evaluated in this study according to Response Evaluation Criteria In Solid Tumors Criteria version 1.1., CA-125 according to published GCIG criteria, and by the investigator on the basis of physical and/or gynaecological examinations.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Nicole Concin, MD principal investigator
Medical University Innsbruck
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ganetespib and Paclitaxel in people with Epithelial Ovarian Cancer and Fallopian Tube Cancer, run by Medical University Innsbruck at 10 sites in 4 countries.
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 26 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 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, France, Austria, Belgium. 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 13 Aug 2019). 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?
Progression Free Survival (PFS) (time frame: Time until progression (median w/o new drug 4 months)). 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 13 Aug 2019.