E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.
The relevant MedDRA codes for recurrent ovarian cancer and fallopian tube cancer are given below. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The principal research question is to see whether adding the drug saracatinib to weekly paclitaxel chemotherapy improves 6 month progression-free survival* in patients with platinum-resistant ovarian cancer.
*The length of time during and after treatment in which a patient is living with a disease that does not get worse. This trial is focusing on the number of patients who achieve a progression-free survival of at least 6 months. |
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E.2.2 | Secondary objectives of the trial |
The secondary research questions are to investigate the safety and tolerability of treating patients with saracatinib and weekly paclitaxel, to measure the overall survival rate of patients at 2 years post treatment, to measure the progression free survival and time to progression, to measure the response rate and duration of response, and to look at the health economics and quality of life implications of treating patients with this regimen. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
SaPPrOC Translational sub-study v1.0 06/07/2010 Diagnostic tumour samples will be assessed for expression of phospho-paxillin and phospho-FAK, markers of Src activation. In addition, whole blood will be taken and separated into plasma and PBMC for identification of potential biomarkers of sensitivity to paclitaxel and Src activation. |
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E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed ovarian, fallopian tube or primary peritoneal cancer
Confirmed relapsed disease AND relapse within the platinum-resistant (progression must not be based on CA125 alone) time-frame, i.e. have progressed within 6 months of platinum therapy. Relapse should ideally have been confirmed radiologically with measurable disease, but patients with CA125 progression plus symptoms indicative of progression will also be allowed to enter
Patients with synchronous tumours e.g. ovarian and endometrial or history of prior malignancy are eligible provided that there is biopsy evidence that the disease measurable on CT and/or MRI is ovarian in origin.
Patients must have archival formalin-fixed paraffin-embedded tissue (or cytological block) from their original diagnosis available for the purposes of translational research (see point sections 4.2 and 20.0)
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 RECIST v1.1 criteria, patients must be evaluable by GCIG CA125 criteria). See Appendices 3-6.
ECOG PS 0-2
Adequate haematological and biochemical function as follows: Neutrophil count > 1.5 x 109/l Platelet count > 100 x 109/l Hb > 9.0 g/dl Serum creatinine < 1.5 x Upper Limit of Normal (ULN) Bilirubin ≤ 1.5 x ULN. In cases of known Gilbert’s syndrome, bilirubin ≤ 2 x ULN is allowed AST or ALT ≤ 2.5 x ULN Alkaline phosphatase < 5 x ULN Prothrombin and activated partial thromboplastin times < 1.5 x ULN (NB values accepted in the form of ratio rather than in seconds where site’s local practice does not give the values in seconds)
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E.4 | Principal 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).
Synchronous primary tumours e.g. ovarian and endometrial with no biopsy evidence of measurable disease of ovarian origin.
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 (as per 5.3.3).
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 (see Appendix 8).
Concurrent autoimmune disorder, e.g. systemic lupus or any demyelinating disease.
Use of immunosuppressive therapy taken within 4 weeks of study entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
6 month progression free survival (PFS) rate based on combined RECIST v1.1/GCIG CA125 criteria. |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
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
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30 days after the last patient has completed all protocol treatment or after stopping treatment due to disease progression. All patients will be followed up as per section 8.2 of the protocol, in order to collect data necessary for the primary and secondary endpoints. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |