Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.
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|ClinicalTrials.gov Identifier: NCT04586335|
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : October 13, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Breast Cancer Solid Tumor Prostate Cancer Endometrial Cancer||Drug: CYH33||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||350 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Open-label, multicenter study which is composed of 2 parts: 1.) dose escalation and 2.) dose expansion. Bayesian optimal interval (BOIN) design will be used to determine the MTD and/or RP2D. Safety, tolerability, PK, PD, and clinical activity will also be evaluated. The CYH33 starting dose of this trial is 20 mg QD in combination with olaparib 300 mg BID. Two additional dose levels of CYH33 at 30 mg QD and 40 mg QD in combination with olaparib 200 mg BID will be evaluated. In the initial dose cohort of 20 mg CYH33 as well as in subsequent dose cohorts 20 and 30 mg QD and 40 mg QD in combination with olaparib 200 mg BID, 3 patients will be initially enrolled at each dose level of CYH33. These evaluable patients will be included into this dose level for decision making on dose selection for the next cohort. 10 mg QD of CYH33 will be evaluated in the combination with olaparib 200 mg BID, according to the BOIN design.|
|Masking:||None (Open Label)|
|Official Title:||Open Label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of CYH33, an Oral PI3K Inhibitor in Combination With Olaparib, an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.|
|Actual Study Start Date :||September 28, 2020|
|Estimated Primary Completion Date :||January 28, 2024|
|Estimated Study Completion Date :||January 28, 2024|
Experimental: CYH33 in Combination with Olaparib
CYH33 in Combination with Olaparib; 20 mg CYH33 QD in combination with olaparib 300 mg BID. Additional dose levels of CYH33 at20 and 30 mg QD and CYH33 at 40 mg QD in combination with olaparib 200 mg BID will be evaluated.
Clinical Activity of CYH33, an Oral α-specific PI3K Inhibitor in Combination with Olaparib, an Oral PARP Inhibitor
Other Name: Olaparib
- Dose Limiting Toxicities (DLT) [ Time Frame: 12 months ]Incidence rate of dose limiting toxicities (DLT) in the first cycle (of 28 days) of each investigated dose levels.
- Tumor objective response rate (ORR) [ Time Frame: 38 months ]Tumor objective response rate (ORR) defined as the sum of complete response (CR) and partial response (PR) as best reported by RECIST version 1.1.
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 38 months ]Number, type, incidence, duration, severity and seriousness of adverse events (AEs) as assessed by CTCAE v5.0
- Disease control rate (DCR) [ Time Frame: 38 months ]Disease control rate (DCR) defined as the sum of CR, PR and stable disease (SD) by RECIST version 1.1. - Progression Free Survival (PFS).
- Pharmacokinetic measures - Plasma concentration time Area Under the Curve [ Time Frame: 12 months ]Measure the variation of CHY33/olaparib concentration in blood plasma as a function of time
- Pharmacokinetic measures - Cmax [ Time Frame: 12 months ]Measure the maximum (peak) plasma concentration(s) of CHY33/olaparib
- Pharmacokinetic measures - Tmax [ Time Frame: 12 months ]Measure of time to reach maximum (peak) plasma concentration(s) following administration of CHY33/olaparib
- Pharmacokinetic measures - CL/F [ Time Frame: 12 months ]Measure apparent total clearance(s) of CHY33/olaparib from plasma after oral administration
- Pharmacokinetic measures - Vz/F [ Time Frame: 12 months ]Measure apparent volume of distribution during terminal phase after administration of CHY33/olaparib
- Pharmacokinetic measures - terminal half- life (t1/2) [ Time Frame: 12 months ]Measure elimination half-life of CHY33/olaparib, when administered in combination
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Key Inclusion Criteria:
Patients eligible for inclusion in this study have to meet all of the following criteria:
- Provide informed consent voluntarily.
- Male and female patients ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age is > 18 years).
Patients with advanced solid tumor who have failed at least one line of prior systemic therapy or for whom standard therapy do not exist and meet the following eligibility for the corresponding part of the study:
- Patient must have a histologically or cytologically confirmed diagnosis of advanced recurrent or metastatic solid tumor.
- At least one measurable lesion as per RECIST 1.1. (Ovarian cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via CA125 GCIG criteria; Prostate cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via PSA response).
- Patients eligible for Part 1 dose escalation: Advanced solid tumors with any DDR gene 1) or PIK3CA 2) mutation who have failed or cannot tolerate standard treatment or currently have no standard treatment.
Patients eligible for Part 2 dose expansion:
- Cohort 1: Advanced solid tumors with any selected DDR3) gene mutation
- Cohort 2: Advanced solid tumors with PIK3CA hotspot mutation
- Cohort 3: Advanced high grade serous ovarian, fallopian tube or primary peritoneal cancer patients with acquired PARP inhibitor resistance4)
- Cohort 4: Advanced solid tumors with any selected DDR3) gene mutation with acquired PARP inhibitor resistance4).
- Cohort 5: Platinum resistant/refractory5) recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
- Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor tissue sample) or blood samples.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Key Exclusion Criteria:
Patients eligible for this study must not meet any of the following criteria:
- Patient has received any anticancer therapy (including chemotherapy, targeted therapy, hormonal therapy, biotherapy, immunotherapy, or other investigational agents.) within 28 days or 5 times of half-lives (whichever is shorter) prior to the first dose of the study treatment or who have not recovered from the side effect of such therapy.
- Patients with contraindication to olaparib treatment or who did not tolerate olaparib previously.
- Patients who had prior treatment with PARP inhibitor, PI3Kα inhibitor, AKT inhibitor or mTOR inhibitor (Part 2 dose expansion cohort 1& 2 only).
- Radical radiation therapy (including radiation therapy for over 25% bone marrow) within 4 weeks prior to the first dose of the investigational product or received local palliative radiation therapy for bone metastases within 2 weeks.
- Any toxicities from prior treatment that have not recovered to baseline or ≤ CTCAE Grade 1 before the start of study treatment, with exception of hair loss.
- Patients with an established diagnosis of diabetes mellitus including steroid-induced diabetes mellitus.
- Major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product or has not recovered from major side effects.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586335
|Contact: Jason Sudia, PhD, MPHemail@example.com|
|Contact: Frank Tan, MD||Base GZ firstname.lastname@example.org|
|United States, Connecticut|
|Yale Cancer Center||Active, not recruiting|
|New Haven, Connecticut, United States, 06519|
|United States, Texas|
|UT Southwestern: Simmons Cancer Center||Active, not recruiting|
|Dallas, Texas, United States, 75390|
|MD Anderson Cancer Center||Active, not recruiting|
|Houston, Texas, United States, 77030|
|Australia, New South Wales|
|Scientia Cancer Centre||Active, not recruiting|
|Sydney, New South Wales, Australia, 2031|
|Integrated Oncology Network PTY LTD||Active, not recruiting|
|Brisbane, Queensland, Australia, 4101|
|Monash Cancer Centre||Active, not recruiting|
|Melbourne, Victoria, Australia, 3168|
|Fudan University - Pudong Medical Center||Recruiting|
|Shanghai, Shanghai, China|
|Contact: Jian Zhang +86 21 5423 7499 email@example.com|
|Principal Investigator: Xiaohua Wu, MD|
|Study Director:||Joan Yu, MD||Haihe Biopharma|
|Responsible Party:||Haihe Biopharma Co., Ltd.|
|Other Study ID Numbers:||
|First Posted:||October 14, 2020 Key Record Dates|
|Last Update Posted:||October 13, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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