Status:
UNKNOWN
Chk2 Inhibitor for Recurrent EpitheliAl periToneal, fallopIan or oVarian cancEr (CREATIVE Phase IA Trial)
Lead Sponsor:
Seoul National University Hospital
Collaborating Sponsors:
Pharos iBio Co., Ltd.
Conditions:
Platinum-resistant Ovarian Cancer
Platinum-refractory Ovarian Carcinoma
Eligibility:
FEMALE
19+ years
Phase:
PHASE1
Brief Summary
This study aims to assess the safety and tolerability of PHI-101 in patients with platinum-resistance/refractory ovarian, fallopian tubal, and primary peritoneal cancer. This study also evaluates the ...
Detailed Description
In this study, a maximum of 6 dose levels (cohorts) were planned for daily oral administration of PHI-101. Subjects who meet the inclusion/exclusion criteria of this study will be enrolled in each coh...
Eligibility Criteria
Inclusion
- Females aged ≥ 19 years at the time of informed consent
- Pregnancy (childbearing potential and planning a pregnancy) and breast-feeding status ① Women of non-childbearing potential, women who are not pregnant or breast-feeding, or women who are not planning a pregnancy during the study
- ② Women of childbearing potential (Section 10.3.2.7.1) who have a confirmed negative pregnancy test at screening and immediately before administration of PHI-101 and agree to use an effective contraceptive method(s) (Section 10.3.2.7.2) required in this protocol for 6 months (24 weeks) from the last dose of PHI-101
- Indication
- ① Histologically or cytologically confirmed ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer
- ② Epithelial malignant tumors diagnosed through local histopathological findings \[WHO Histological Classification, 2014\]
- : except LGSC, mucinous carcinoma of the ovary, MMMT, and LAP, which are classified as LCOH, \[NCCN Guideline version 2.2019\].
- LAP = low malignant potential (ovarian borderline epithelial tumor); LCOH = less common ovarian histopathology; LGSC = low-grade serous carcinoma; MMMT = malignant mixed Mullerian tumor (carcinosarcoma); NCCN Guideline = National Comprehensive Cancer Network Guideline; WHO Histological Classification = World Health Organization Histological Classification ③ Platinum-refractory cancer\* or platinum-resistance cancer†
- Disease progression during platinum-based antineoplastic therapy, † Disease progression within 6 months (24 weeks) from completion of platinum-based antineoplastic therapy ④ Inoperable subjects who are refractory to, cannot receive, or refuse standard of care, which is currently known to be clinically beneficial ⑤ Subjects with ≥ 1 measurable lesion or nonmeasurable, but evaluable lesion that meets \[RECIST version 1.1\] RECIST = Response Evaluation Criteria in Solid Tumors
- Expected life expectancy ≥ 12 weeks
- \[ECOG PS\] ≤ 1 ECOG PS = Eastern Cooperative Oncology Group Performance Status
- Subjects who have adequate hepatic, renal, and hematological function confirmed by the following laboratory tests (a re-test will be allowed during the screening period) ANC ≥ 1,500/mm3 (without administration of G-CSF within 2 weeks prior to baseline) Hb ≥ 10.0 g/dL (without transfusion within 2 weeks prior to baseline) Platelet count ≥ 75,000/mm3 (without transfusion within 2 weeks prior to baseline) Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 3.0 x ULN\* (≤ 5 x ULN for patients with liver metastases or hepatocellular carcinoma) Serum creatinine (or CrCl) Serum creatinine ≤ 1.5 x ULN CrCl ≥ 60 mL/min (by Cockcroft-Gault equation)
- Prior antineoplastic therapy and treatment ① Prior cytotoxic chemotherapy ≤ 5 times
- ② Reversible side effects from prior antineoplastic therapy (operation, drug, radiation therapy, etc.)\* resolved to \[CTCAE version 5.0\] grade 1 or better
- \* Subjects should not have had major surgery, antineoplastic therapy or experimental therapy, or direct radiation therapy on hematopoietic site within 4 weeks prior to baseline and should not be administered nitrosoureas or mitomycin-C within 6 weeks prior to baseline.
- CTCAE = Common Terminology Criteria for Adverse Events
- Subjects who voluntarily decided to participate and provided written consent after they were given sufficient explanation of this study
- Subjects who are able to understand the study procedures and restrictions and willing to comply with them during the study
Exclusion
- 1\) Subjects with known or suspected hypersensitivity or intolerance to the active ingredient or excipients of PHI-101 2) Subjects considered ineligible or unable to participate in this study according to the investigator's judgement for other reasons
- Medical history or current medical condition and disease 3) Subjects with the following cardiac insufficiency or cardiovascular disease (but not limited to):
- Evidence of myocardial ischemia or myocardial infarction within 12 weeks prior to baseline
- \[NYHA Functional Classification\] ≥ II NYHA = New York Heart Association ③ LVEF \< 50% confirmed by ECHO or MUGA scan LVEF = left ventricular ejection fraction; ECHO = echocardiography; MUGA = Multi-gated acquisition blood pool scintigraphy
- Clinically significant cardiac arrhythmia that is uncontrolled by the adequate and optimal treatments
- ⑤ Corrected QT (QTc)\* interval \> 450 msec (for both men and women) or long QT syndrome (or family history)
- \* QT interval (QTcF) corrected using Fridericia's formula will be used. In case of bundle branch block, the Bazett's formula will be used (QTcB).
- 4\) Subjects with the following gastrointestinal diseases that affect intake or absorption of the drug (but not limited to):
- Dysphagia
- Paralysis of intestine and intestinal obstruction
- ③ Gastrointestinal surgery that has a clinically significant effect on absorption of the drug: gastrotomy, small intestinal fistula, extensive small bowel resection, etc. (except for simple anastomosis)
- ④ Autoimmune or inflammatory disease that involves the entire gastrointestinal system or small intestines: coeliac disease, intestinal graft versus host disease, Behcet's syndrome, scleroderma involving the gastrointestinal tract, Crohn's disease, ulcerative colitis, etc.
- 5\) Lung diseases (but not limited to):
- New or progressive dyspnea, cough, and fever
- ② Planned diagnosis of interstitial lung disease, or interstitial pneumonia
- ③ Pulmonary fibrosis 6) Hematologic malignancy including lymphoma 7) Metastasis:
- Central nervous system metastasis or brain metastasis ② Bone metastasis 8) Infectious disease (but not limited to):
- Severe infectious disease requiring administration of antibiotics, antivirals, etc. that may affect the safety and efficacy assessments during the study
- Active (overt) infectious disease that is uncontrolled by the adequate and optimal treatments as determined by the investigator 9) Known positive human immunodeficiency virus (HIV) 10) Active hepatitis B\* or active hepatitis C†
- HBsAg positive with HBV DNA detected † Anti-HCV positive with HCV RNA detected (qualitatively) 11) Unintentional weight loss \> 10% within 12 weeks prior to informed consent 12) History of alcohol or other drug abuse within 1 year (52 weeks) prior to informed consent
- Subjects who received, are receiving, or cannot stop the following therapy (medication/non-medication) 13) Subjects who need antineoplastic therapy\* other than the IP during the study participation (Point radiation to alleviate bronchial obstruction, skin lesion, etc. is allowed).
- \* Surgery, radio(chemo)therapy, cytotoxic chemotherapy, targeted therapy (small molecule drug, monoclonal antibody), immuno-oncology drug (biological drug), hormone therapy, etc.
- 14\) Subjects who received (used) other investigational study product or device within 2 weeks or 5 half-lives prior to informed consent (whichever is shorter) 15) Subjects on drugs (nonprescription drug, herb, homeopathy, etc.) that have a significant effect on the assessment of kinetics (metabolism, excretion, etc. in the body) or efficacy and safety of the IP within 2 weeks prior to informed consent as determined by the investigator
Key Trial Info
Start Date :
December 17 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2023
Estimated Enrollment :
36 Patients enrolled
Trial Details
Trial ID
NCT04678102
Start Date
December 17 2020
End Date
December 31 2023
Last Update
June 26 2023
Active Locations (1)
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1
Seoul National University Hospital
Seoul, South Korea