scholarly journals A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Soo Jin Park ◽  
Suk-Joon Chang ◽  
Dong Hoon Suh ◽  
Tae Wook Kong ◽  
Heekyoung Song ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Dose Escalation ◽  
Recurrent Ovarian Cancer ◽  
Dose Escalation Study ◽  
Checkpoint Kinase ◽  
Link Type ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Checkpoint Kinase 2

Abstract Background PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. Methods Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. Discussion PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. Trial registration ClinicalTrials.gov Identifier: NCT04678102.

A randomized double-blind phase III trial comparing vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD plus placebo in patients with platinum-resistant ovarian cancer (PROCEED).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5613-TPS5613 ◽  
Author(s):  
R. Wendel Naumann ◽  
Lucy Gilbert ◽  
Anthonette M. Miller ◽  
Hong Ma ◽  
Sharad A. Ghamande ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Folate Receptor ◽  
Performance Status ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

TPS5613 Background: Folate receptor (FR) is expressed on the majority of epithelial ovarian cancers and FR expression appears to be a negative prognostic factor in this setting. Vintafolide (EC145) is a folate-conjugate designed to selectively deliver desacetylvinblastine monohydrazide (DAVLBH) to FR-expressing cells. 99mTc-Etarfolatide (EC20) is a technetium-labeled folate that identifies FR-expressing tumors. In a phase 2 study comparing vintafolide + PLD with PLD alone, the combination demonstrated a statistically and clinically significant delay in PFS (5.0 months) compared with PLD alone (2.7 months) in women with platinum-resistant ovarian cancer (Naumann et al, ASCO 2011). Data also indicated that 99mTc-etarfolatide may have utility for selecting patients most likely to benefit from vintafolide therapy. Methods: This is an international, randomized, double-blind, placebo-controlled phase 3 study of PLD ± vintafolide therapy compared in patients with primary or secondary platinum-resistant ovarian cancer (NCT01170650). Key eligibility criteria include: ≥18 years, pathology-confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, prior platinum-based chemotherapy, a RECIST v1.1 measureable lesion, and ECOG performance status 0 or 1. At baseline, patients undergo 99mTc-Etarfolatide imaging to identify FR-positive lesions and are subsequently randomized to the vintafolide ± PLD. PLD (50 mg/m2) adjusted for Ideal Body weight is administered on day 1 of a 4-week cycle and treatment continues until the maximum allowable cumulative dose (550 mg/m2) is reached or until disease progression or intolerable toxicity. Vintafolide (2.5 mg) or placebo is administered on days 1, 3, 5, 15, 17, and 19 of a 4-week cycle and treatment can continue for up to 20 cycles or until unacceptable toxicity or disease progression. The primary objective is to assess PFS based on investigator assessment (RECIST v1.1) in FR positive patients. Secondary objectives include OS, safety/tolerability, overall response rate, and disease control rate. Enrollment to the study is currently ongoing. Clinical trial information: NCT01170650.

scholarly journals A Phase IB open-label, dose-escalation study of NUC‑1031 in combination with carboplatin for recurrent ovarian cancer

2021 ◽  
pp. clincanres.4403.2020
Author(s):  
Farasat Kazmi ◽  
Shibani Nicum ◽  
Rene L Roux ◽  
Laura Spiers ◽  
Chat Gnanaranjan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dose Escalation ◽  
Recurrent Ovarian Cancer ◽  
Open Label ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Label Dose

scholarly journals PRO-002, a phase Ib dose-escalation study of NUC-1031 with carboplatin for recurrent ovarian cancer

2017 ◽  
Vol 28 ◽  
pp. v345 ◽  
Author(s):  
S.P. Blagden ◽  
A. Sukumaran ◽  
L. Spiers ◽  
V.K. Woodcock ◽  
A. Lipplaa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dose Escalation ◽  
Recurrent Ovarian Cancer ◽  
Dose Escalation Study ◽  
Phase Ib

Feasibility of bevacizumab combined with gemcitabine in treatment of platinum-resistant epithelial ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17064-e17064 ◽  
Author(s):  
Ai Kogiku ◽  
Shoji Nagao ◽  
Kazuhiro Suzuki ◽  
Kasumi Yamamoto ◽  
Tokihiro Senda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Recurrent Ovarian Cancer ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Chemotherapy Patients ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

e17064 Background: We assessed the efficacy and safety of a combination chemotherapy comprising gemcitabine and bevacizumab for the treatment of platinum-resistant recurrent ovarian cancer. Here we report the results of the interim analysis. Methods: Eligible patients showed recurrent, measurable tumors that had progressed within 6 months after the completion of platinum-based chemotherapy. Patients received gemcitabine (1000 mg/m2) on days 1and 8 and bevacizumab (15 mg/kg) on day1 every 3 weeks until disease progression or unacceptable toxicity levels were observed. The primary end point was the proportion of patients who completed three cycles of scheduled chemotherapy. Results: Twelve patients were enrolled in this study and three patients are still undergoing chemotherapy. The proportion of patients who completed three cycles of chemotherapy was 77.8 % (7/9), and response rate was 66.7 % (6/9). Grade ≥ 3 neutropenia, thrombocytopenia, and hypertension were observed in five, one, and one patients, respectively. There was no GI perforation or death in our study. Conclusions: Combination chemotherapy of comprising gemcitabine and bevacizumab was safe and effective in patients with platinum-resistant recurrent ovarian cancer. Therefore, it is important to continue this study. Clinical trial information: 000016619.

scholarly journals Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e041463
Author(s):  
Anita Mansouri ◽  
Naomi McGregor ◽  
Rachel Dunn ◽  
Sam Dobbie ◽  
Jane Holmes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Antiangiogenic Therapy ◽  
Single Agent ◽  
Unmet Need ◽  
Dropout Rate ◽  
Weekly Paclitaxel ◽  
Type I ◽  
Link Type ◽  
Platinum Based Chemotherapy

IntroductionPatients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months.Methods and analysisEthics and disseminationThis study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150.Trial registration numberISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.

Sign in / Sign up

Export Citation Format

Share Document