Ovarian, fallopian tube or primary peritoneal cancer of clear cell, endometrioid or high grade serous subtype or carcinosarcoma MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10052171 Term: Peritoneal carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) Me
Conditions
Interventions
Product Name: Paclitaxel
Product Code: N/A
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
CAS Number: 33069-62-4
Other descriptive name: Taxol
Concentration
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent prior to admission to the study and initiation of any study procedures in accordance with ICH-GCP guidelines and to the local legislation 2. Females = 18 years of age 3. Pathological diagnosis of ovarian, fallopian tube or primary peritoneal cancer, of clear cell, endometrioid or high grade serous subtype or carcinosarcoma. Local tumour board/MDT histological review is required and in mixed tumours more than 50% endometrioid, clear cell or high grade serous elements are required to define the predominant histology 4. Platinum-resistant disease (recurrence within 6 months of last platinum treatment), Patients having received at least one prior line of chemotherapy. Carboplatin and weekly paclitaxel are permitted as first line therapy 5. Measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 (Appendix A) by CT or MRI 6. Fresh tumour biopsy during screening is compulsory if judged technically feasible by radiologist 7. Patients with a history of brain metastasis are eligible as long as all the following criteria are met: brain metastases must have been treated, have no evidence of progression or haemorrhage after treatment, have been off dexamethasone for 4 weeks prior to first study treatment, and no ongoing requirement for dexamethasone or anti-epileptic drugs 8. Available blocks for (IHC) and tissue microarray (TMA) or, if no block is available, 20 ordinary unstained slides (5µm sections) will be acceptable 9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 10. Adequate organ and bone marrow function: a. Absolute neutrophil count (ANC) = 1.5 x 109/L b. Platelets = 100 x 109/L c. Haemoglobin = 9 g/dL d. Total bilirubin = 1.5 x upper limit of normal (ULN) ( 1 year before the screening visit OR b. Are surgically sterile OR c. If of childbearing potential, patient agrees to practice one of the following from informed consent to 90 days after the last dose of study treatment (or longer, as mandated by local labelling [e.g. Summary of Product Characteristics]): i) Practice 1 highly effective method of contraception and 1 additional effective barrier method at the same time. Permitted methods of contraception are specified in section 6.7.2 ii) Practice true abstinence where this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence [e.g. calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together 12. For women of child-bearing potential, negative blood serum pregnancy test within 14 days prior to the first study treatment 13. Able to swallow oral medication Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Numb
Exclusion criteria
Exclusion criteria: 1. Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, mTORC1/2 inhibitors or mTORC1 inhibitors 2. Prior weekly single agent paclitaxel 3. Known allergy to paclitaxel and/or any excipients of investigational medicinal products that, in the investigator’s opinion, precludes study treatment on clinical and/or safety grounds 4. Treatment with strong inhibitor/s and/or inducer/s of cytochrome P450 (CYP) 3A4 or CYP2C8 within 7 days of study treatment 5. Central nervous system (CNS) metastasis, for patients who have brain metastases, they will be eligible if their brain metastases must have been treated, have no evidence of progression or haemorrhage after treatment, have been off dexamethasone for 4 weeks prior to first study drug administration, and no ongoing requirement for dexamethasone or anti-epileptic drugs 6. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the study 7. Known human immunodeficiency virus infection 8. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection 9. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol 10. German sites only: Unable to be regularly followed up for any reason (geographic, familiar, social, psychological, housed in an institution e.g. prison because of a court agreement or administrative order) 11. German sites only: Subjects that are dependent on the sponsor (and/or contracted body e.g. CRO) or investigational site as well as on the investigator 12. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study treatment, or previously diagnosed with another malignancy and evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection 13. Breast feeding or pregnant 14. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK228. In addition, patients with enteric stomata are also excluded 15. Treatment with any investigational products, chemotherapy or radiotherapy within 28 days, or major surgery within 21 days of study treatment 16. History of any of the following within the last 6 months before administration of the first dose of study treatment: a. Ischemic myocardial event, including angina requiring therapy and artery revascularisation procedures b. Ischemic cerebrovascular event, including transient ischemic attack and artery revascularisation procedures c. Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) d. Placement of a pacemaker for control of rhythm e. New York Heart Association (NYHA) Class III or IV heart failure (See Appendix B) f. Pulmonary embolism 17. Significant active cardiovascular or pulmonary disease including: a. Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of anti-hypertensive agents to control hypertension before first dose of study treatment is allowed b. Pulmonary hypertension c. Uncontrolled asthma or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effectiveness of TAK228 plus weekly paclitaxel with weekly paclitaxel alone as treatments for women with advanced/recurrent ovarian, fallopian tube or primary peritoneal cancer resistant to platinum chemotherapy, based on progression free survival (PFS). PFS is the length of time during and after a treatment that each patient lives with the cancer but it does not grow significantly. In a clinical trial, measuring the progression-free survival is one way to see how well each treatment works.;Secondary Objective: To compare the effectiveness of TAK228 plus weekly paclitaxel and weekly paclitaxel alone as treatments for women with advanced/recurrent ovarian, fallopian tube or primary peritoneal cancer resistant to platinum chemotherapy, based on the following: - Progression free survival (PFS) at 24 weeks - Overall response rate (ORR). This means the proportion of patients for whom the cancer significantly shrinks (called partial response) or disappears completely (called complete response) after a treatment - Duration of response (DoR), meaning that in patients with partial or complete response, the length of time between that response and the cancer significantly growing - Time to progression (TTP). This means the length of time measured from a patient entering the study and the cancer growing significantly or spreading to other parts of the body - Clinical Benefit Rate (CBR). This is similar to ORR but also includes patients for whom the cancer neither significantly grows or shrinks (cal;Primary end point(s): Progression free survival (PFS; as assessed by RECIST v1.1), defined as time from study entry to first evidence of disease progression or death due to any cause ;Timepoint(s) of evaluation of this end point: Every 8 weeks/2 treatment cycles, then at end of treatment and 3 monthly during follow up until progressive disease (PD) as documented by RECIST v1.1 (or death, if this occurs sooner) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression Free Survival (PFS; as assessed by RECIST v1.1) at 24 weeks, defined as time from study entry to first evidence of disease progression or death due to any cause. 2. Overall Response Rate (ORR; as assessed by RECIST v1.1) defined by complete response (CR) or partial response (PR) 3. Duration of response (DOR), defined as time from study entry to change in response from CR or PR to stable disease (SD) or progressive disease (PD) (as assessed by RECIST v1.1). 4. Time to progression (TTP), defined as time from study entry to first evidence of disease progression or death due to any cause. 5. Clinical Benefit Rate (CBR; as assessed by RECIST v1.1) defined as CR, PR or SD for at least 4 months 6. Response according to CA125 levels (response has occurred if there is at least a 50% reduction in CA125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment 7. Overall Survival (OS) defined as time from study entry to death due to any cause or to study termination 8. Safety and tolerability as assessed by adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 9. Quality of Life as assessed by EORTC QLQ-C30 and EORTC QLQ-OV28 ;Timepoint(s) of evaluation of this end point: 1. 24 weeks/after 6 treatment cycles 2. As per E5-1 3. As per E5-1 4. As per E5-1 5. As per E5-1 6. Day 1 of each treatment cycle, then at end of treatment visit and 3 monthly during follow up until progression or death (whichever occurs first) 7. Every protocol visit until death 8. As per 7 above 9. Day 1 of each treatment cycle, then at end of treatment visit | — |
Countries
Germany, United Kingdom
Contacts
Public ContactClinical Trials Section
Imperial College London
Outcome results
None listed