Phase II and Pharmacological Study with Wee-1 inhibitor AZD1775 Combined with Carboplatin in Patients with p53 Mutated Epithelial Ovarian Cancer that Show Early Relapse (<3 months) or Progression during Standard First Line Treatment with Carboplatin - Paclitaxel Combination Therapy. With an additional safety and preliminary anti-tumor activity cohort of Wee-1 inhibitor AZD1775 Combined with Carboplatin in Patients with p53 Mutated Epithelial Ovarian Cancer, non-small cell lung cancer (NSCLC), sm
- Conditions
- (non-)small cell lung cancercervical cancerendometrial cancerlung cancerovarian cancerp53 mutated epithelial ovarian cancer10038595
- Registration Number
- NL-OMON47848
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 56
Inclusion criteria for phase II POP trial:
1. p53 mutated (determined by IHC and later by sequencing) epithelial ovarian cancer
2. measurable disease on CT scan or elevated CA-125 levels that can be monitored
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;Additional inclusion criteria for the safety and activity cohort:
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 (, 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. See chapter 10 for additional information and Appendix XI +XII
5. Able and willing to undergo a fresh tumor biopsy (if p53 status is already known , tumor biopsy is still mandatory) .
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.
4. more than 2 prior cytotoxic chemotherapy regimens
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Proof of concept trial:<br /><br>To determine the safety and preliminary anti-tumor activity of MK-1775 in<br /><br>combination with carboplatin in p53 mutated epithelial ovarian cancer in a 21<br /><br>day schedule.<br /><br><br /><br>Additional safety and preliminary activity cohorts:<br /><br>To determine the safety and preliminary anti-tumor activity (RECIST 1.1) of<br /><br>AZD1775 in combination with carboplatin in p53 mutated epithelial ovarian<br /><br>cancer, NSCLC, SCLC, cervical, and endometrial cancer, in a 21 day schedule</p><br>
- Secondary Outcome Measures
Name Time Method <p>Phase II POP trial:<br /><br>- To determine the pharmacokinetics of MK-1775 in plasma and of carboplatin in<br /><br>plasma and ultrafiltrates.<br /><br>- To determine pharmacodynamic changes induced by MK-1775 in combination with<br /><br>carboplatin in both surrogate tissues (skin) and tumor tissue.<br /><br><br /><br>Additional safety and preliminary activity cohorts:<br /><br>- To determine the time to progression.<br /><br>- To determine the pharmacodynamic changes induced by AZD1775 in combination<br /><br>with carboplatin in circulating tumor cells (CTC).</p><br>