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
Overview
- Phase
- Phase 1
- Intervention
- Ganetespib
- Conditions
- Epithelial Ovarian Cancer
- Sponsor
- Medical University Innsbruck
- Enrollment
- 133
- Locations
- 10
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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.
Investigators
Nicole Concin
Univ.-Prof. Dr.
Medical University Innsbruck
Eligibility Criteria
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
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
Arms & Interventions
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.
Intervention: Ganetespib
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.
Intervention: Paclitaxel
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
Intervention: Paclitaxel
Outcomes
Primary Outcomes
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.