Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer

Inclusion criteria:

• Confirmed relapsed ovarian, fallopian tube or primary peritoneal cancer AND relapse within the platinum-resistant (progression must not be based on Cancer Antigen 125 (CA125) alone) time-frame, i.e. have progressed within 6 months of platinum therapy.

• Patients need not have received prior taxane; if patients have received prior taxane, the interval since treatment must be known. Patients will be stratified as <6 months or 6+ months taxane interval/no prior taxane.

• Patients will generally have received at least 2 lines of prior chemotherapy, but may enter if they have relapsed within 6 months of first line therapy. Patients may have received prior liposomal doxorubicin, although this is NOT a requirement. The treatment immediately prior to study entry need not be platinum-based.

• Measurable or evaluable disease (if not measurable by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 criteria, patients must be evaluable by Gynecologic Cancer InterGroup (GCIG) CA125 criteria).

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2

• Adequate haematological and biochemical function.

Exclusion criteria

• Prior administration of weekly paclitaxel.

• Tumours of malignant mixed mesodermal (MMMT) or mucinous subtypes, or non-epithelial ovarian cancers (e.g. Brenner tumours, Sex-cord tumours).

• Unresolved bowel obstruction.

• Chemotherapy within the preceding 3 weeks.

• Radiotherapy within the preceding 3 weeks.

• Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer.

• Known leptomeningeal involvement or intracranial disease.

• Evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung disease).

• Resting ECG with measurable QTc interval of >480 msec at 2 or more time points within a 24 hour period.

• Pregnant or lactating females.

• Fertile women of childbearing potential not willing to use highly effective contraception for the duration of trial treatment and for at least 6 months after the last administration of saracatinib +/- paclitaxel.

• Inability or unwillingness to give informed consent.

• Ongoing active infection or a documented history of HIV infection, Hepatitis B or C.

• Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.

• Concurrent autoimmune disorder, e.g. systemic lupus or any demyelinating disease.

• Use of immunosuppressive therapy or corticosteroids taken within the 4 weeks prior to study entry and during the treatment period.