p53 mutated epithelial ovarian cancer (after first line standard therapy), non-small cell lung cancer, small cell lung cancer, cervical and endometrial cancer MedDRA version: 20.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT
Conditions
Interventions
Product Name: MK-1775
Product Code: MK-1775
Pharmaceutical Form: Capsule
INN or Proposed INN: AZD1775
CAS Number: 855365-80-7
Sponsors
Netherlands Cancer Institute (NKI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. p53 mutated (determined by IHC and later by sequencing) epithelial ovarian cancer 2. measurable disease on CT scan 3. patients previously received standard 1st line platinum therapy (combined with paclitaxel) for epithelial ovarian cancer, and showed recurrence on or within 3 months of this treatment 4. age > 18 years 5. WHO performance status lower or equal to 1 1. histological or cytological proof of advanced epithelial ovarian cancer, NSCLC, SCLC, cervical and endometrial cancer (with proven p53 mutation). 2. previously treated with (standard) (1st) line platinum-based therapy (combined with paclitaxel in case of ovarian cancer ), and showed recurrence on or within 6 months after the end of this treatment. 3. Patients are allowed to have received second line non-platinum containing therapy after recurrence on 1st line treatment. No more than 2 lines of pre-treatment with cytotoxic chemotherapy are allowed. 4. Eligible patients will have p53 mutation determined by sequencing of exons 2-10. 5. Able and willing to undergo a tumor biopsy (if p53 status is already known, tumor biopsy is still mandatory). 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 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. symptomatic cerebral or leptomeningeal metastases 2. current participation or previous participation in a study with an investigational compound, or chemo- and/or radiotherapy within 28 days of receiving first dose of study medication 3. patient must not have prior radiation therapy to more than 30% of the bone marrow and must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy. Additional exclusion criteria for safety and activity cohort: 1. More than 2 lines pre-treatment with cytotoxic chemotherapy are not allowed. Only the first line will be carboplatin or cisplatin containing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Safety will be assessed on a continuous basis; Preliminary anti-tumor activity will be assessed by CT-scan every 2 cycles (once per 6 weeks) and tumor markers (if applicable) every cycle (every 3 weeks). ; Main Objective: To determine the safety and preliminary anti-tumor activity of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer in a 21 day schedule. Additional safety and preliminary anti-tumor activity cohort: To determine the safety and preliminary anti-tumor activity (RECIST 1.1) of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer, NSCLC, SCLC, cervical, and endometrial cancer, in a 21 day schedule. ; Secondary Objective: - To determine the pharmacokinetics of AZD1775 in plasma and of carboplatin in plasma and ultrafiltrates. - To determine pharmacodynamic changes induced by AZD1775 in combination with carboplatin in both surrogate tissues (skin). -To determine the time to progression. Secondary objectives safety and preliminary anti-tumor activity cohort: - To determine the time to progression. - To determine the pharmacodynamic changes induced by AZD1775 in combination with carboplatin in circulating tumor cells (CTC). ; Primary end point(s): Phase II proof-of-concept trial: - to determine the safety and preliminary anti-tumor activity of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer in 21 day schedule. Additional safety and preliminary anti-tumor activity cohort: -to determine the safety and preliminary anti-tumor activity (RECIST 1.1) of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer, NSCLC, SCLC, cervical and endome | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): secondary objectives proof-of-concept trial: - To determine the pharmacokinetics (PK) of AZD1775 in plasma and of carboplatin in plasma and ultrafiltrates. - To determine pharmacodynamics (PD) changes induced by AZD1775 in combination with carboplatin in surrogate tissues (skin) - To determine the time to progression. Secondary objectives safety and preliminary anti-tumor activity cohort: - To determine the time to progression. - To determine the pharmacodynamic changes induced by AZD1775 in combination with carboplatin in circulating tumor cells (CTC). ; Timepoint(s) of evaluation of this end point: -PK and PD: at day 1 of cycle 1 -Time to progression: every 2 cycles (6 weeks) | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Netherlands Cancer Institute
Outcome results
None listed