advanced ovarian cancer MedDRA version: 16.1 Level: PT Classification code 10070908 Term: Ovarian cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.1 Level: PT Classification code 10070907 Term: Ovarian cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: carboplatin
Product Name: carboplatin
Pharmaceutical Form: Intravesical solution/solution for injection
INN or Proposed INN: Carboplatin
Other descriptive name: CARBOPLATIN
Trade Name: pa
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria • Patients with advanced stage (FIGO III-IV), histologically confirmed and documented epithelial ovarian carcinoma • Patients eligible for neoadjuvant carboplatin/paclitaxel chemotherapy prior to surgical debulking (phase 1 or 2) OR patients with relapsed or progressive ovarian cancer after first line treatment eligible for palliative carboplatin/paclitaxel chemotherapy (phase 1 only) • If an exploratory laparotomy was performed at diagnosis, patients are only eligible if aggressive tumour debulking procedures were not performed. Only minimal tumour resection for the purpose of diagnosis and palliation are allowed. Aggressive tumour debulking procedures include total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, with or without lymphadenectomy (phase 2 only) • Measurable tumour according to RECISTv1.1 or GCIG CA125 criteria (phase 2 only) • Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0-2 • Age = 18 years • Laboratory Requirements - within 7 days prior to enrolment: • absolute neutrophil count [ANC] =1.5 x 109/L • platelets > 100 x 109/L • haemoglobin >9g/dl. Patients may be transfused or use erythropoietin to maintain haemoglobin values = 9 g/dl. • hepatic function: bilirubin =1.5×upper limit of normal (ULN), AST/ALT=2.5×ULN • estimated creatinine clearance = 60ml/min • Before patient registration/randomization, written informed consent for the trial must be given according to ICH/GCP, and national/local regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: Exclusion criteria • Prior chemotherapy, immunotherapy, targeted agents or radiotherapy to abdomen or pelvis (phase 2 only) • Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study. • Metformin within 4 weeks prior to enrolment. • Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer (phase 2 only) • Symptomatic CNS metastasis • Pre-existing peripheral neuropathy = CTC grade 2. • Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. • Women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the study and for 6 months after the last study medication. • Known hypersensitivity to any of the study drugs or excipients. • Serious active infection requiring i.v. antibiotics at enrolment. • Unstable medical conditions. • Evidence of any other medical conditions, physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: The primary objective of this phase of the study is to determine the recommended phase II dose of metformin in combination with neoadjuvant carboplatin/paclitaxel chemotherapy in patients with advanced ovarian cancer. Phase II: The primary objective of the second phase of this study is to determine the activity of adding metformin to carboplatin/paclitaxel neoadjuvant chemotherapy in patients with advanced stage ovarian cancer. Response will be measured according to the GCIG criteria incorporating RECIST 1.1 criteria and/or CA-125 levels as appropriate.;Secondary Objective: Phase I: The secondary objectives of this phase of the study are: • To document the safety profile of metformin in combination with carboplatin/paclitaxel chemotherapy • To document the influence of metformin on the pharmacokinetics of carboplatin/paclitaxel chemotherapy Phase II: The secondary objectives of the second phase of this study are: • To determine safety and tolerability • To describe the effect of metformin on the likelihood of complete tumour debulking • To describe the effect of metformin on the likelihood of complete pathological response • To describe the effect of metformin on response in subsets of patients with measurable and non-measurable disease • To evaluate patient outcome • To explore the effect of metformin treatment on the tumour expression of immunohistochemical biomarkers. • To explore the effect of metformin treatment on the levels of serum biomarkers • To explore the concentration of metformin in tumour cells ;Primary end point(s): Phase I: Recommended phase II dose based on dose-limiting toxicities and maximum tolerated dose of metformin in combination with carboplatin/paclitaxel. Phase II: The primary end-point is objective response rate in patients with measureable disease and CA-125 response as defined by the Gynaecologic Cancer Intergroup (GCIG) for non-measurable disease. ;Timepoint(s) of evaluation of this end point: Phase 1: | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I: • Plasma levels of carboplatin, paclitaxel and metformin • Worst grade of AE and laboratory events as determined by CTCAEv4 criteria Phase II: • All adverse events and laboratory events coded and graded by the CTCAEv3 criteria • Percentage of patients in which complete debulking is achieved (residual disease <1cm) • Percentage of patients with a complete pathological response • Objective tumour response by RECIST version 1.1 in patients with measurable disease • Objective tumour response by CA-125 criteria in patients without measurable disease • Progression free survival and overall survival distributions • Exploratory analysis of paired pre-and post treatment immunohistochemical tumour tissue biomarker expression as described in translational research section • Exploratory analysis of paired pre-and-post treatment serum biomarker levels as described in the translational research section • Exploratory analysis of metformin concentrations in tumour cells as described in the translational research section ;Timepoint(s) of evaluation of this end point: Phase I: • Plasma levels will be measured during the first 3 days of cycles 1 and 2 • AE and laboratory events will be measured during cycles 1 and 2 Phase II: • AE and laboratory events during all cycles of therapy • Percentage of complete debulking and pathological complete response at time of operation (after 3 cycles) • Objective tumour response at time of CT-scan • Progression free survival and overall at 6-12 months • Exploratory translational research analyses after completion of the trial | — |
Countries
Netherlands
Contacts
Public ContactMedical Oncology
University Medical Center Groningen
Outcome results
None listed