| Eligibility |
Inclusion Criteria:
- Patients must meet the following criteria to be eligible for study entry:
- 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, undifferentiated epithelial ovarian
cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer
- Platinum-sensitive relapse >6months 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 lines
- Measurable or evaluable disease according to RECIST 1.1
- ECOG performance status 0-1
- Adequate functions of the bone marrow
- Platelets = 100 x 109/L
- Absolute neutrophil count (ANC) = 1.5 x 109/L
• Adequate function of the organs
- Creatinine < 2 mg/dl (<177 µmol/L)
- Total bilirubin = 1.5 x upper limit of normal (= 2.0 in patients with known Gilberts
syndrome) OR direct bilirubin = 1 x ULN
- 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
- 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.
- Participants 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 non-childbearing potential.
Non-childbearing potential is defined as follows (by other than medical reasons):
- = 45 years of age and has not had menses for >1 year
- 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
- 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.
- 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)
Exclusion Criteria:
- Patients who meet any of the following criteria will be excluded from study entry:
- 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
asymptomatic 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 York Heart Association (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 excipients 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
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