GANNET53: Ganetespib in Metastatic, p53-mutant, Platinum-resistant Ovarian Cancer

June 25, 2019 updated by: Nicole Concin, Medical University Innsbruck

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
133

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Medical University Innsbruck, Department for Gynaecology and Obstetrics
  • Belgium
      • Leuven, Belgium, 3000
        • Katholieke Universiteit Leuven, Dept. of Gynaecologic Oncology
  • France
      • Caen, France, 14076
        • Centre de Lutte Contre le Cancer François Baclesse
      • Lyon, France, 69373
        • Centre anticancereux Leon Berard
      • Paris, France, 45004
        • Assistance Publique - Hôpitaux de Paris Medical Oncology Department
  • Germany
      • Berlin, Germany, 10117
        • Universitätsmedizin Berlin Charité, Dept. for Gynecology
      • Dresden, Germany, 01069
        • University Hospital Carl Gustav Carus Dresden, Department of Gynaecology and Obstetrics
      • Essen, Germany, 45136
        • Kliniken Essen Mitte, Evang. Huyssens-Stiftung / Knappschaft GmbH Department of Gynaecologic Oncology
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf Dept. of Gynecology and Gynecologic Oncology
      • Magdeburg, Germany, 39106
        • Otto-von-Guericke-Universität Magdeburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Ganetespib + Paclitaxel
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.
Drug: Paclitaxel
Drug: Ganetespib
ACTIVE_COMPARATOR: Paclitaxel
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
Drug: Paclitaxel

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Time until progression (median w/o new drug 4 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University Innsbruck

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European Commission

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nicole Concin, MD, Medical University Innsbruck

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 4, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 4, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 16, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 13, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GANNET53
  • 2013-003868-31 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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