| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Platinum-sensitive relapsed ovarian cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with ovarian cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the progression-free survival (PFS) by RECIST 1.1 |
|
| E.2.2 | Secondary objectives of the trial |
To determine the progression-free survival (PFS)
To determine the post-progression progression-free survival (PFS2)
To determine the time to first subsequent therapy (TFST)
To determine the time to second subsequent therapy (TSST)
To determine the safety of the therapy
To determine the objective response rate (ORR)
To determine the patient reported outcome
To determine the overall survival (OS) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Ability to understand and willingness to sign and date a written informed consent document
• Female patients ≥ 18 year of age
• High-grade serous, high grade endometrioid, undifferentiated epithelial ovarian, or carcinosarcoma, fallopian tube or primary peritoneal cancer
• Platinum-sensitive relapse > 6 months after previous platinum-based treatment (calculated from the first day of the last cycle of the last platinum based chemotherapy until the date of progression confirmed according to RECIST 1.1 on imaging)
• No limits in number of prior treatment lines
• Measurable or evaluable disease according to RECIST 1.1
• ECOG performance status 0-1
• Adequate functions of the bone marrow:
o Platelets ≥ 100 x 109/L
o Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Adequate function of the organs:
o Creatinine < 2 mg/dl (<177 µmol/L)
o Total bilirubin ≤ 1.5 x upper limit of normal (≤ 2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
o SGOT/SGPT (AST/ALT) ≤ 2.5 x upper limit of normal unless liver metastases are present, in which case they must be ≤ 5 x ULN
o 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; except the proteinuria is clearly related to a catheter in the urinary system.
• Adequate coagulation parameter: aPTT ≤ 1.5 x ULN (patients on heparin treatment must have an aPTT between 1.5-2.5 x ULN), or INR ≤ 1.5. (In patients receiving anticoagulants (such as warfarin) INR must be between 2.0 and 3.0 in two consecutive measurements 1-4 days apart).
• Participant receiving corticosteroids (dose < 10 mg/day methylprednisolone equivalent), including inhaled steroids, may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.
• Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
• Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):
o ≥ 45 years of age and has not had menses for >1 year
o Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating
hormone value in the postmenopausal range upon screening evaluation
o Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with
medical records of the actual procedure or confirmed by imaging. Tubal ligation must be confirmed with medical records of the actual procedure,
otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days
after the last dose of study treatment. See below for a list of acceptable birth control methods. Information must be captured appropriately within
the site’s source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
o Birth Control: Participants of childbearing potential who are sexually active and their partners must agree to the use of a highly effective form of
contraception throughout their participation beginning with time of consent, during the study treatment and for 180 days after last dose of study
treatment(s):
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral route
• Intravaginal route
• Transdermal route
Progestogen-only hormonal contraception associated with inhibition of ovulation
• Oral
• Injectable
• Implantable
Intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomized partner
Sexual abstinence, if the preferred and usual lifestyle of the subject
• Participant must agree to not breastfeed (or store breast milk for use) during the study or for 180 days afer the last dose of study treatment.
• Haemoglobin ≥8.5 g/dl (patients may not receive a transfusion within 4 weeks prior to initiating study treatment)
• Able to take oral medications
• Availability of archival ovarian cancer tissue from primary diagnosis (delivery of FFPE block or slides is prerequisite for randomisation)
|
|
| E.4 | Principal exclusion criteria |
• Ovarian tumours with low malignant potential (i.e. borderline tumours)
• Any prior radiotherapy to the pelvis or abdomen, or any radiotherapy encompassing > 20 % of the bone marrow within 2 weeks, or any radiotherapy within 1 week prior to Day 1 of protocol therapy.
• Surgery (including open biopsy and traumatic injury) within 4 weeks prior to first dose of Ganetespib, or anticipation of the need for major surgery during study treatment
• Minor surgical procedures, within 24 hours prior to the first study treatment
• Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Any serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
• Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (> 325 mg/day).
• Patients with a history of diagnosis, detection or treatment of any prior malignancies ≤ 2 years prior to initiating protocol therapy, except: basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated.
• Clinically significant gastro-intestinal (GI) tract abnormalities that may increase the risk for GI bleeding and / or perforation including but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding; inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), history of bowel obstruction within 1 year prior to first study treatment (excluding postoperative, i.e. within 4 weeks post surgery), other GI condition with increased risk of perforation such as recurrence deeply infiltrating into the muscularis or mucosa of the rectosigmoid or the mucosa of the bladder, or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
• Non-healing wound or non-healing bone fracture
• Patients with symptomatic brain or leptomeningeal metastases (patients who are asyptomatic since treatment of brain or leptomeningeal metastases, eg after irradiation, are eligible)
• Left ventricular ejection fraction (LVEF) defined by ECHO below the institutional lower limit of normal
• Cerebrovascular accident (CVA)/ stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤ 6 months prior to first study treatment.
• Significant cardiac disease: New Yourk Heart Assiciation (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary atrial or ventricular cardiac arrhythmias
• History of prolonged QT syndrome, or family member with prolonged QT syndrome
• QTc interval > 470 msec when 3 consecutive ECG values are averaged
• Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia 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)
• History of evidence of haemorrhagic disorders, patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorders, coagulopathy or tumour involving major vessels.
• Participation in another clinical study with experimental therapy within 28 days before start of treatment.
• Participant must not be simultaneously enrolled in any interventional clinical trial.
• Women who are pregnant or are lactating
• Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution eg. prison because of a court agreement or administrative order)
• Subjects that are dependent on the sponsor/CRO or investigational site as well as on the investigator.
• History of known hypersensibility against any medication used in the study
• Intolerance / Hypersensitivity reactions to components and exipients of study drugs
• Peripheral neuropathy of grade >2 per NCI CTCAE, version 4.03, within 4 weeks prior to randomisation
• 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
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS) by RECIST 1.1 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Evaluation will be done 6 months after LPI, this is expected in Q1 2020 |
|
| E.5.2 | Secondary end point(s) |
PFS according to pre-defined subgroups
Post-progression PFS (PFS2)
Time to First Subsequent Therapy (TFST)
Time to Second Subsequent Therapy (TSST)
Safety: Adverse events (AEs), measure according to NCI CTCAE, version 4.03
Objective response rate (ORR)
Patient-reported outcome (PRO)
Overall survival (OS)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Evaluation will be done 1 to 1.5 years after the evaluation of the primary end point, this is therefore expected in Q1 - Q3 2021 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Biomarker analysis on DNA, RNA and protein level |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
Print
