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

NCT02012192 | Terminated Phase 1 Results DMC

• 2 other identifiers: GANNET532013-003868-31
• Study Type: interventional
• Target: 133
• Locations: 4 countries
• Sites: 10

Brief 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 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.

Conditions

Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Keywords

High-grade serous; high-grade endometrioid; undifferentiated

Outcome Measures

Primary Outcomes (1)

• 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.

  Time until progression (median w/o new drug 4 months)

Study Arms (2)

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.

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

Drug: Paclitaxel

Interventions

Ganetespib DRUG

Ganetespib + Paclitaxel

Paclitaxel DRUG

Ganetespib + Paclitaxel; Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University Innsbruck: lead
• European Commission: collaborator

Study Sites (10)

Medical University Innsbruck, Department for Gynaecology and Obstetrics

Innsbruck, 6020, Austria

Location

Katholieke Universiteit Leuven, Dept. of Gynaecologic Oncology

Leuven, 3000, Belgium

Location

Centre de lutte contre le cancer Francois Baclesse

Caen, 14076, France

Location

Centre Anticancereux Léon Bérard

Lyon, 69373, France

Location

Assistance Publique - Hôpitaux de Paris Medical Oncology Department

Paris, 45004, France

Location

Universitätsmedizin Berlin Charité, Dept. for Gynecology

Berlin, 10117, Germany

Location

University Hospital Carl Gustav Carus Dresden, Department of Gynaecology and Obstetrics

Dresden, 01069, Germany

Location

Kliniken Essen Mitte, Evang. Huyssens-Stiftung / Knappschaft GmbH Department of Gynaecologic Oncology

Essen, 45136, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Dept. of Gynecology and Gynecologic Oncology

Hamburg, 20246, Germany

Location

Otto-von-Guericke-Universität Magdeburg

Magdeburg, 39106, Germany

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Disorders of Sex Development

Interventions

STA 9090; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Urogenital Abnormalities; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Prof. Dr. Nicole Concin
• Organization: Medical University of Innsbruck

nicole.concin@i-med.ac.at

+43 512 504

Study Officials

• Nicole Concin, MD

  Medical University Innsbruck

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.-Prof. Dr.

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 16, 2013
• Study Start: July 4, 2014
• Primary Completion: November 30, 2017
• Study Completion: December 4, 2017
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2019-06

Locations

BE (1); AU (1); FR (3); DE (5)