Spots Global Cancer Trial Database for A Study of HC-7366 to Establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

Study Description

Brief Summary: This is a first in human, multicenter, open label, Phase 1a and 1b dose-escalation and dose-expansion study to establish the maximum tolerated dose, recommended Phase 2 dose, and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose escalating fashion in subjects with advanced solid tumors. Up to 40 subjects will be enrolled into the Phase 1a dose-escalation part of the study. The study will be conducted in the United States at approximately 7 to 10 sites. Every effort will be made to ensure approximately 50% of all subjects enrolled into Phase 1a of this study are subjects with the tumors of special interest including squamous cell carcinoma of the head and neck, colorectal cancer, non-small cell lung cancer, and transitional cell carcinoma of the bladder. Subjects with other solid tumor types are also eligible provided study selection criteria are met and they do not exceed 50% of all enrolled subjects. All subjects in Phase 1b will enroll with clear cell renal cell carcinoma. The Phase 1a study will follow a traditional 3+3 design. The starting dose level will be 10 mg QD, escalating to 20, 40, 75, 125, and 150 mg QD as safety allows. All doses are to be administered in the fasting state with water at least 1 hour before food or at least 2 hours after food. The Phase 1b dose-expansion will be at a single dose level of 75 mg based on the safety, tolerability, PK/PD results from Phase 1a to obtain additional safety and preliminary efficacy information. At the discretion of the safety monitoring committee and sponsor, the cohort may be expanded to enroll additional patients and/ or 1-2 additional cohorts will be opened. Up to 30 subjects may be enrolled in the Phase 1b portion of the study at the 75 mg dose. Replacement patients will be enrolled if necessary. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors, discontinuation of treatment for other protocol allowed reason (eg, subject refusal), any other administrative reasons, or after 2 years of treatment, whichever occurs first. For scheduling purposes, dosing in Phase 1a and 1b will occur in 3 week cycles and computed tomography scans will be conducted once every 6 weeks from Cycle 1/Day 1, with the first postbaseline scan after 6 weeks of dosing (precycle 3) until confirmed disease progression, death, start of new anticancer therapy, withdrawal of consent, or end of study, whichever occurs first.

Detailed Description: Subjects of Phase 1a and 1b are to spend Cycle 1/Day 1 (C1D1) in the clinic followed by an optional overnight stay for safety monitoring and PK sampling. Subjects will be hospitalized (optional) for administration of the first 2 doses: C1D1 and Cycle 1/Day 2 (C1D2). After the initial optional hospital stay at the start of study, subjects will be seen in the outpatient clinic on Days 8, 15, and 21 of Cycle 1 and thereafter, on the first day of each cycle for physical and laboratory assessments, adverse event (AE) and dosing compliance monitoring, and PK C3-C6; the End of Treatment visit will also be in-person in the outpatient clinic. An overnight stay for Cycle 1/Day 21 (C1D21) to C2D1 is also optional. Subjects will be allowed to go home after having a 12-hour PK sample draw in the clinic and will be asked to return to the clinic on C1D2 (for a safety check with a PK sample draw and an electrocardiogram (ECG) prior to dosing. Subjects of Phase 1a who discontinue before the first postbaseline CT scan for reasons other than disease progression, a treatment-related AE, or dose limiting toxicity (DLT) prior to completion of the DLT evaluation period will be replaced to ensure an adequate safety assessment at each dose level. Subjects of Phase 1b who discontinue before the first postbaseline CT scan for reasons other than disease progression, or a treatment-related AE will be replaced and will be censored for efficacy; however, enrollment will continue to include enough subjects at each dose level in order to complete safety and efficacy assessments of that dose level. Each subject in Phase 1a and 1b will be treated for a maximum of 2 years and followed for a maximum of 2 years. Six dose-escalation levels are planned for subjects in the Phase 1a part of the study. Dose escalation will follow a traditional 3+3 design. A minimum of 3 subjects will be enrolled in each cohort sequentially, with expansion to 6 subjects in each cohort as needed to determine the DLT. For each cohort, the first subject is a sentinel subject. Sentinel subjects will be dosed and followed for 4 days to assess safety and tolerability. If deemed safe and well tolerated, the remainder of the cohort (N=2) will be enrolled. If none of the first 3 subjects in a cohort experiences a study treatment related DLT during the first 21 days (DLT evaluation period), the next cohort may be enrolled. Before applying the dose escalation rules, 3 subjects in a given dose level must have received a minimum of 75% of the planned dose and have been evaluated for toxicity, unless one or more subjects experiences a DLT within the first 21 days. If the first 3 DLT-evaluable subjects within a cohort experience no DLTs during the DLT-evaluation period, the next cohort may enroll. In the case a subject does not receive a minimum of 75% of the planned dose, for any reason other than a DLT (ie, lost to follow-up), the subject may be replaced. DLT's will be reviewed by the Safety Monitoring Committee (SMC) when the planned number of subjects of Phase 1a part of the study complete their DLT observation period using the dose-escalation rules. If the MTD is not reached even at the maximum dose level (150 mg QD is well tolerated), a higher dose level may be evaluated based on the SMC recommendations after a comprehensive review of the safety, PK, and efficacy data generated from the study.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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