Renal Cell CarcinomaPhase 1NCT04834778
A Study of HC-5404-FU to Establish the Maximum Tolerated Dose (MTD)
A Phase 1 study testing HC-5404-FU in people with Renal Cell Carcinoma and Gastric Cancer, run by HiberCell, Inc. at 4 sites in United States.
Trial summary
Study HC-404-FCP-2011 is a first in human, Phase 1a, multi-center, open-label study to establish the maximum tolerated dose (MTD) and evaluate the safety and tolerability of oral dosing of HC-5404-FU in a dose-escalating fashion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma, Gastric Cancer, Metastatic Breast Cancer
- What is being tested?
- HC-5404-FU
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesUnited States
- Study dates
- 8 Jun 2021to 30 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a signed informed consent form prior to any study specific procedures or treatment
- Be ≥18 years of age (male or female) at the time of consent
- Have 1 of the following histologically or cytologically confirmed tumor types with qualifying characteristics, and have received a minimum of 2 (and no more than 5) lines of prior therapy for metastatic (Stage IV) disease:
- RCC (renal cell carcinoma - clear cell or papillary)
- SCLC (small cell lung cancer) OR have received a minimum of 3 (and no more than 5) lines of prior therapy for metastatic (Stage IV) disease:
- GC (gastric adenocarcinoma)
Show all 37Show fewer
- Human epidermal growth factor receptor positive (HER2+) MBC (metastatic breast cancer)
- Other solid tumors (e.g., non-small cell lung cancer, colorectal cancer, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (e.g., pancreatic cancer, glioblastoma, hepatocellular carcinoma)
- Note: Subjects with RCC and GC are a priority and should constitute approximately 50% (12 subjects) of the enrolled popululation. Enrollment of all others will be capped when reaching a combined 50%, in order to maintain 12 slots for subjects with RCC and GC.
- Have at least 1 radiologically measurable lesion as per RECIST v 1.1, defined as a lesion that is at least 10 mm in longest diameter or lymph node and that is at least 15 mm in short axis imaged by CT scan or magnetic resonance imaging (MRI) and obtained by imaging within 28 days prior to screening. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- Have resolution of all previous treatment related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (≤ Grade 2) and alopecia. If the subject received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention
- Provided there are suitable and accessible lesions, no biopsy contraindications, minimal risk of complications and a positive informed decision, subject as are willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality, for assessment of biomarker status. Two biopsies will be necessary: at baseline (within 30 days prior to first dose) and within 7 days after Cycle 3/Day 1.
- Newly obtained biopsy specimens are preferred to archived samples and formalin- fixed, paraffin-embedded block specimens are preferred to slides. In the event a fresh pre-treatment biopsy is not able to be provided, the most recent archival biopsy must be provided in its place
- Have Eastern Cooperative Oncology Group performance status of 0 or 1 and sustained between screening and initiation of dosing on Day 1
- QT interval corrected for heart rate using Fridericia's (QTcF) method ≤450 msec
- Have an albumin level of ≥3 g/dL at screening
- Have life expectancy of 3 months or greater as determined by the treating physician
- Have adequate organ function within 15 days prior to first administration of study drug on Day 1, as defined by meeting all of the following criteria:
- Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels >1.5 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN or ≤5 × ULN for subjects with known hepatic metastases
- Fasting serum glucose within normal range and hemoglobin A1c ≤8%
- Thyroid function tests (thyroid stimulating hormone [TSH] within normal limits for subjects with normal thyroid function and free thyroxine [FT4]) within normal limits for subjects on thyroid treatment
- Have adequate renal function within 15 days prior to first administration of study drug on Day 1, as defined by creatinine ≤1.5 × ULN and creatinine clearance ≥30 mL/min, as per the below Cockcroft Gault formula
- Have adequate hematologic function within 15 days prior to first administration of study drug on Day 1, as defined by meeting all of the following criteria:
- Hemoglobin ≥9 g/dL (uncorrected by red blood cell transfusion or erythropoietin support)
- Absolute neutrophil count ≥1.5 × 109/L
- Platelet count ≥100 × 109/L
- Have adequate coagulation function within 15 days prior to first administration of study drug on Day 1, as defined by either of the following criteria:
- International normalized ratio (INR) <1.5 × ULN OR for subjects receiving warfarin or low molecular weight heparin, the subject must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy
- Activated partial thromboplastin time (aPTT) <1.5 × ULN unless subject is receiving anticoagulant therapy, provided prothrombin time or aPTT is within therapeutic range of intended use of anticoagulants
- Female subject of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subject of childbearing potential must be willing to use an adequate form of contraception from the first dose of study medication through 90 days after the last dose of study drug
- Female subject must agree not to breastfeed and not to donate ova starting at screening and throughout the study treatment, and for 90 days after the last dose of study drug
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or for the time partner is breastfeeding throughout the study period and for 90 days after the last dose of study drug
- Male subject with female partner(s) of childbearing potential must not donate sperm during the treatment period and for at least 90 days after the last dose of study drug
- Male subject with female partner(s) of childbearing potential should agree to use a highly effective method of contraception during the treatment period and for at least 90 days after the last dose of the study drug
- Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment or who has not recovered from adverse reactions due to a previously administered agent or major surgery
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (≤30 mg/day of hydrocortisone, ≤10 mg/day of prednisone, ≤2 mg/day of dexamethasone, or equivalent) may be approved after consultation with the sponsor
- Has taken a medication that is a strong CYP3A4 inhibitor or inducer within 4 weeks of the first dose of treatment (see Appendix 12)
- Has known history of active tuberculosis
- Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Show all 20Show fewer
- Has known active Hepatitis B (anti hepatitis B surface antibody, anti hepatitis B core antibody, hepatitis B surface antigen [HBsAg]) or Hepatitis C (hepatitis C antibody) infection
- Has a current diagnosis of severe acute respiratory syndrome coronavirus (SARS CoV) 2 infection confirmed by reverse transcription polymerase chain reaction (PCR) test. Subject needs to have a negative PCR test at screening and a negative PCR test within 14 days prior to the first dose of study treatment
- Has a history of clinically severe autoimmune disease, or a history of organ transplant
- Has insulin dependent (Type I) diabetes or poorly controlled Type II diabetes (per clinical discretion) with hemoglobin A1c >8%
- Has known additional malignancy that is progressing or required active treatment within previous 5 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy, superficial bladder cancer, or in situ cervical cancer. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease free for at least 5 years
- Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using systemic steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Has a history of interstitial lung disease, pneumonitis within 12 months prior to screening or current pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has a history or ongoing clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome, symptomatic or uncontrolled arrhythmia, congestive heart failure, baseline ECG abnormalities, including, but not limited to, QTc prolongation (prolonged QTcF defined as ≥450 msec) or any Class III or IV cardiac disease as defined by the New York Heart Association Functional Classification
- Has overt or latent disorders of the exocrine pancreas (such as acute or chronic pancreatitis of any etiology) or chronic (including autoimmune) gastrointestinal disorders such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus, scleroderma, Sjogren's syndrome, and polyarteritis nodosa
- Has a known psychiatric or substance abuse disorder(s) that would interfere with informed consent or cooperation with the requirements of the trial
- Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the prescreening or screening visit through 90 days after the last dose of study drug
- Is a first degree relative of the investigator, staff, or study sponsor.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Baylor University Medical Center
Dallas, Texas, 75246
Karmanos Cancer Institute
Detroit, Michigan, 48201
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
HealthPartners Cancer Care Center
Saint Paul, Minnesota, 55101
About this study
Official title: A Multicenter, Open-label, Phase 1a Study of HC-5404-FU in Subjects With Advanced Solid Tumors
Study HC-404-FCP-2011 is a first in human, Phase 1a, multi-center, open-label study to establish the maximum tolerated dose (MTD) and evaluate the safety and tolerability of oral dosing of HC-5404-FU in a dose-escalating fashion. Up to 36 qualified subjects at 3 to 5 US sites, who have specific tumor types of renal cell carcinoma (RCC), gastric cancer (GC), metastatic breast cancer (MBC), small cell lung cancer (SCLC), and other solid tumors (e.g., non-small cell lung cancer, colorectal cancer, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (e.g., pancreatic cancer, glioblastoma, hepatocellular carcinoma) will receive HC-5404-FU. Every effort will be made to ensure approximately 50% of all subjects enrolled will be subjects with RCC and GC. The starting dose level is 25 mg twice daily (BID), escalating to 50, 100, and 200 mg BID as safety allows, following the Bayesian Optimal Interval (BOIN) design. The safety monitoring committee (SMC) will evaluate the DLTs and cumulative safety and PK data at the end of each cohort. Based on the SMC recommendations after a comprehensive review of PK and safety data for 200 mg BID dose, higher dose levels will be evaluated, starting with 400 mg BID. The dose will escalate to 600 mg and then 900 mg following the BOIN design starting with 1 subject at each escalated dose, until the MTD is reached or the sponsor or SMC declares the dose most appropriate for clinical development. This Phase 1a will be expanded into a Phase 1b/2a study through a protocol amendment and will then assess the dose and tumor type(s) selected in Phase 1a as the most appropriate for further clinical development. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors (iRECIST), subject withdrawal, any other administrative reasons, or after 2 years of treatment, whichever occurs first. Efficacy will be assessed via Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1); computed tomography (CT) scans will be conducted every 6 weeks. Safety, including occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), and biomarker parameters will also be assessed.
Read the detailed description
HC 5404-FU will be orally administered BID with food or within 30 minutes of completing a meal, starting at 25 mg, with doses escalating to 50, 100, 200, 400, 600 and 900 mg BID as safety allows. Up to 24 subjects will be enrolled to ensure 12 subjects complete the study at the estimated MTD of HC 5404-FU. Dosing will occur in 3-week cycles. Subjects are to spend Cycle 1/Day 1 (C1D1) in the clinic followed by an overnight stay for safety monitoring and PK sampling. Subjects will be hospitalized for administration of first 3 doses: C1D1 am and pm doses, and Cycle 1/Day 2 (C1D2) am dose; on Days 8, 15, and 21 the am dose will be taken in the clinic after the planned PK samples. All other doses are to be self administered at home. After the initial hospital stay at the start of study, subjects will be seen in outpatient clinic on Days 8, 15, and 21 of Cycle 1 for PK assessment and thereafter, the first day of each cycle for physical and laboratory assessments, adverse event (AE), and dosing compliance monitoring; the end of treatment visit will also be in person in outpatient clinic.
Following completion of the treatment period of the study, subjects will be monitored for survival up for up to 24 months after the last post treatment follow-up visit.
Dose escalation will follow the Bayesian Optimal Interval (BOIN) design. The decision to escalate to the next dose level will be based on safety assessments after all subjects of a cohort have reached the end of Cycle 1/Day 21 (DLT evaluation period). The safety monitoring committee (SMC) will be responsible for dose escalation decisions, including whether to modify the dose escalation based on the DLT observations and review of available PK data.
The target toxicity rate of 30%, with limits of 0.236 to 0.359 for escalation/de escalation, will be employed to determine the MTD. With these predefined parameters, when the observed toxicity rate in a dose level is less than 0.236, the dose for the next cohort can escalate. If the observed toxicity rate is higher than 0.359, the dose will de escalate. Otherwise, the dose remains the same.
Individual subjects may be considered for treatment at a higher dose than the dose to which they were initially assigned after subject has completed 2 cycles of treatment and 1 postbaseline CT scan and maintained at least a stable disease (SD) response. In order to escalate a dose level, the subject must have tolerated his/her current dose level without experiencing a DLT, and the dose level to which the subject is planned to be escalated must have completed a DLT evaluation period, not exceeded the MTD, and been declared safe. Each subject can go through 2 dose escalations and do not need to go through a DLT evaluation period for either escalation. Intrasubject dose escalation will be considered on a case-by-case basis, each case to be assessed and approved by the sponsor.
- Conditions
- Renal Cell Carcinoma, Gastric Cancer, Metastatic Breast Cancer, Small-cell Lung Cancer, Other Solid Tumors
- Being tested
- HC-5404-FU
- Keywords
- RCC, GC, MCA, SCLC, Phase 1, First in human, HC-5404-FU, HC-5404
- Medical subject headings
- Carcinoma, Renal Cell, Stomach Neoplasms, Breast Neoplasms, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HC-5404-FUDrug
Also called HC-5404
HC 5404-FU (hemi fumarate salt of HC 5404) is a novel, highly selective, and potent PERK inhibitor. Preclinical pharmacological studies demonstrated high specificity of HC 5404-FU to PERK and decreased viability of tumor cells. HC 5404-FU will be orally administered BID every day with food or within 30 minutes of completing a meal, starting at 25 mg, with doses escalating to 50, 100, 200, 400, 600, and 900 mg BID as safety allows for each 3-week treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - 25 mg | Experimental | 25 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 2 - 50 mg | Experimental | 50 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 3 - 100 mg | Experimental | 100 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 4 - 200 mg | Experimental | 200 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 5 - 400 mg | Experimental | 400 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 6 - 600 mg | Experimental | 600 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 7 - 900 mg | Experimental | 900 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
| Cohort 8 - 300 mg | Experimental | 300 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle Receives: Drug: HC-5404-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of MTD of HC-5404-FU
When orally administered in a dose escalating fashion in subjects with selected, advanced solid tumors
Measured: Within 18 months of last patient enrolled
Occurrence of dose-limiting toxicities (DLTs)
Measured: Within 18 months of last patient enrolled
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related TEAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Measured: Within 18 months of last patient enrolled
Incidence of TEAEs leading to premature discontinuation
Measured: Within 18 months of last patient enrolled
Incidence of significant laboratory abnormalities, based on hematology, serum chemistry, and urinalysis test results
Measured: Within 18 months of last patient enrolled
Incidence of abnormalities observed in 12 lead ECG parameters
Measured: Within 18 months of last patient enrolled
Incidence of abnormalities observed in vital signs measurements and physical examinations
Measured: Within 18 months of last patient enrolled
Secondary outcomes (16)
Area under the plasma concentration versus time curve from time 0 until last measurable concentration (AUC0 last)
Measured: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 to 12 hours postdose (AUC0 12)
Measured: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC0 ∞)
Measured: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve over a dosing interval (AUC0 t)
Measured: Within 24 months of last patient enrolled
Peak plasma concentration (Cmax)
Measured: Within 24 months of last patient enrolled
Time of the maximum observed plasma concentration (tmax)
Measured: Within 24 months of last patient enrolled
Apparent total clearance (CL/F) of plasma concentration
Measured: Within 24 months of last patient enrolled
Apparent volume of distribution during the terminal phase (Vz/F) of plasma concentration
Measured: Within 24 months of last patient enrolled
Apparent terminal elimination half life (t1/2) of plasma concentration
Measured: Within 24 months of last patient enrolled
Accumulation ratio based on AUC0 t (ARAUC) of plasma concentration
Measured: Within 24 months of last patient enrolled
Linearity ratio (LR) of plasma concentration
Measured: Within 24 months of last patient enrolled
Overall response rate (ORR) to HC-5404-FU using iRECIST
Measured: Within 24 months of last patient enrolled
Duration of response (DOR) to HC-5404-FU using iRECIST
Measured: Within 24 months of last patient enrolled
Time to treatment failure (TTF)
Measured: Within 24 months of last patient enrolled
Progression-free survival (PFS) using iRECIST
Measured: Within 24 months of last patient enrolled
Overall response (OS) using iRECIST
Measured: Within 24 months of last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2021
- Study start8 Jun 2021
- Primary completion7 Dec 2023
- Study completion30 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- HiberCell, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Responsible party
- Sponsor
- Investigators
- Jose Iglesias, MD, Study director, Consultant Chief Medical Officer for HiberCell, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04834778
- Sponsor's protocol ID
- HC-404-FCP-2011
- Status last verified
- Mar 2024
- First submitted
- 2 Apr 2021
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Phase 1a Study of HC-5404-FU in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04834778
- Acronym / sponsor ID
- HC-404-FCP-2011
- Conditions
- Renal Cell Carcinoma, Gastric Cancer, Metastatic Breast Cancer, Small-cell Lung Cancer, Other Solid Tumors
- Keywords
- RCC, GC, MCA, SCLC, Phase 1, First in human, HC-5404-FU, HC-5404
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- HiberCell, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Study start
- 8 Jun 2021 (actual)
- Primary completion
- 7 Dec 2023 (actual)
- Study completion
- 30 Jan 2024 (actual)
- First posted
- 8 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study HC-404-FCP-2011 is a first in human, Phase 1a, multi-center, open-label study to establish the maximum tolerated dose (MTD) and evaluate the safety and tolerability of oral dosing of HC-5404-FU in a dose-escalating fashion. Up to 36 qualified subjects at 3 to 5 US sites, who have specific tumor types of renal cell carcinoma (RCC), gastric cancer (GC), metastatic breast cancer (MBC), small cell lung cancer (SCLC), and other solid tumors (e.g., non-small cell lung cancer, colorectal cancer, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (e.g., pancreatic cancer, glioblastoma, hepatocellular carcinoma) will receive HC-5404-FU. Every effort will be made to ensure approximately 50% of all subjects enrolled will be subjects with RCC and GC. The starting dose level is 25 mg twice daily (BID), escalating to 50, 100, and 200 mg BID as safety allows, following the Bayesian Optimal Interval (BOIN) design. The safety monitoring committee (SMC) will evaluate the DLTs and cumulative safety and PK data at the end of each cohort. Based on the SMC recommendations after a comprehensive review of PK and safety data for 200 mg BID dose, higher dose levels will be evaluated, starting with 400 mg BID. The dose will escalate to 600 mg and then 900 mg following the BOIN design starting with 1 subject at each escalated dose, until the MTD is reached or the sponsor or SMC declares the dose most appropriate for clinical development. This Phase 1a will be expanded into a Phase 1b/2a study through a protocol amendment and will then assess the dose and tumor type(s) selected in Phase 1a as the most appropriate for further clinical development. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors (iRECIST), subject withdrawal, any other administrative reasons, or after 2 years of treatment, whichever occurs first. Efficacy will be assessed via Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1); computed tomography (CT) scans will be conducted every 6 weeks. Safety, including occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), and biomarker parameters will also be assessed.
Detailed description
HC 5404-FU will be orally administered BID with food or within 30 minutes of completing a meal, starting at 25 mg, with doses escalating to 50, 100, 200, 400, 600 and 900 mg BID as safety allows. Up to 24 subjects will be enrolled to ensure 12 subjects complete the study at the estimated MTD of HC 5404-FU. Dosing will occur in 3-week cycles. Subjects are to spend Cycle 1/Day 1 (C1D1) in the clinic followed by an overnight stay for safety monitoring and PK sampling. Subjects will be hospitalized for administration of first 3 doses: C1D1 am and pm doses, and Cycle 1/Day 2 (C1D2) am dose; on Days 8, 15, and 21 the am dose will be taken in the clinic after the planned PK samples. All other doses are to be self administered at home. After the initial hospital stay at the start of study, subjects will be seen in outpatient clinic on Days 8, 15, and 21 of Cycle 1 for PK assessment and thereafter, the first day of each cycle for physical and laboratory assessments, adverse event (AE), and dosing compliance monitoring; the end of treatment visit will also be in person in outpatient clinic.
Following completion of the treatment period of the study, subjects will be monitored for survival up for up to 24 months after the last post treatment follow-up visit.
Dose escalation will follow the Bayesian Optimal Interval (BOIN) design. The decision to escalate to the next dose level will be based on safety assessments after all subjects of a cohort have reached the end of Cycle 1/Day 21 (DLT evaluation period). The safety monitoring committee (SMC) will be responsible for dose escalation decisions, including whether to modify the dose escalation based on the DLT observations and review of available PK data.
The target toxicity rate of 30%, with limits of 0.236 to 0.359 for escalation/de escalation, will be employed to determine the MTD. With these predefined parameters, when the observed toxicity rate in a dose level is less than 0.236, the dose for the next cohort can escalate. If the observed toxicity rate is higher than 0.359, the dose will de escalate. Otherwise, the dose remains the same.
Individual subjects may be considered for treatment at a higher dose than the dose to which they were initially assigned after subject has completed 2 cycles of treatment and 1 postbaseline CT scan and maintained at least a stable disease (SD) response. In order to escalate a dose level, the subject must have tolerated his/her current dose level without experiencing a DLT, and the dose level to which the subject is planned to be escalated must have completed a DLT evaluation period, not exceeded the MTD, and been declared safe. Each subject can go through 2 dose escalations and do not need to go through a DLT evaluation period for either escalation. Intrasubject dose escalation will be considered on a case-by-case basis, each case to be assessed and approved by the sponsor.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - 25 mg | Experimental | Drug: HC-5404-FU25 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 2 - 50 mg | Experimental | Drug: HC-5404-FU50 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 3 - 100 mg | Experimental | Drug: HC-5404-FU100 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 4 - 200 mg | Experimental | Drug: HC-5404-FU200 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 5 - 400 mg | Experimental | Drug: HC-5404-FU400 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 6 - 600 mg | Experimental | Drug: HC-5404-FU600 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 7 - 900 mg | Experimental | Drug: HC-5404-FU900 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
| Cohort 8 - 300 mg | Experimental | Drug: HC-5404-FU300 mg capsules of HC-5404-FU administered orally twice a day with food or within 30 minutes of completing a meal of each 3-week treatment cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Have a signed informed consent form prior to any study specific procedures or treatment
- Be ≥18 years of age (male or female) at the time of consent
- Have 1 of the following histologically or cytologically confirmed tumor types with qualifying characteristics, and have received a minimum of 2 (and no more than 5) lines of prior therapy for metastatic (Stage IV) disease:
- Note: Subjects with RCC and GC are a priority and should constitute approximately 50% (12 subjects) of the enrolled popululation. Enrollment of all others will be capped when reaching a combined 50%, in order to maintain 12 slots for subjects with RCC and GC.
- Have at least 1 radiologically measurable lesion as per RECIST v 1.1, defined as a lesion that is at least 10 mm in longest diameter or lymph node and that is at least 15 mm in short axis imaged by CT scan or magnetic resonance imaging (MRI) and obtained by imaging within 28 days prior to screening. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Key exclusion criteria (20 listed)
- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment or who has not recovered from adverse reactions due to a previously administered agent or major surgery
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (≤30 mg/day of hydrocortisone, ≤10 mg/day of prednisone, ≤2 mg/day of dexamethasone, or equivalent) may be approved after consultation with the sponsor
- Has taken a medication that is a strong CYP3A4 inhibitor or inducer within 4 weeks of the first dose of treatment (see Appendix 12)
- Has known history of active tuberculosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HC-5404-FUAlso: HC-5404HC 5404-FU (hemi fumarate salt of HC 5404) is a novel, highly selective, and potent PERK inhibitor. Preclinical pharmacological studies demonstrated high specificity of HC 5404-FU to PERK and decreased viability of tumor cells. HC 5404-FU will be orally administered BID every day with food or within 30 minutes of completing a meal, starting at 25 mg, with doses escalating to 50, 100, 200, 400, 600, and 900 mg BID as safety allows for each 3-week treatment cycle. | Drug | Cohort 1 - 25 mg, Cohort 2 - 50 mg, Cohort 3 - 100 mg, Cohort 4 - 200 mg, Cohort 5 - 400 mg, Cohort 6 - 600 mg, Cohort 7 - 900 mg, Cohort 8 - 300 mg |
Primary outcome
Determination of MTD of HC-5404-FU
Time frame: Within 18 months of last patient enrolled
When orally administered in a dose escalating fashion in subjects with selected, advanced solid tumors
Occurrence of dose-limiting toxicities (DLTs)
Time frame: Within 18 months of last patient enrolled
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related TEAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Time frame: Within 18 months of last patient enrolled
Incidence of TEAEs leading to premature discontinuation
Time frame: Within 18 months of last patient enrolled
Incidence of significant laboratory abnormalities, based on hematology, serum chemistry, and urinalysis test results
Time frame: Within 18 months of last patient enrolled
Incidence of abnormalities observed in 12 lead ECG parameters
Time frame: Within 18 months of last patient enrolled
Incidence of abnormalities observed in vital signs measurements and physical examinations
Time frame: Within 18 months of last patient enrolled
16 secondary outcomes
Area under the plasma concentration versus time curve from time 0 until last measurable concentration (AUC0 last)
Time frame: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 to 12 hours postdose (AUC0 12)
Time frame: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC0 ∞)
Time frame: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve over a dosing interval (AUC0 t)
Time frame: Within 24 months of last patient enrolled
Peak plasma concentration (Cmax)
Time frame: Within 24 months of last patient enrolled
Time of the maximum observed plasma concentration (tmax)
Time frame: Within 24 months of last patient enrolled
Apparent total clearance (CL/F) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Apparent volume of distribution during the terminal phase (Vz/F) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Apparent terminal elimination half life (t1/2) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Accumulation ratio based on AUC0 t (ARAUC) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Linearity ratio (LR) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Overall response rate (ORR) to HC-5404-FU using iRECIST
Time frame: Within 24 months of last patient enrolled
Duration of response (DOR) to HC-5404-FU using iRECIST
Time frame: Within 24 months of last patient enrolled
Time to treatment failure (TTF)
Time frame: Within 24 months of last patient enrolled
Progression-free survival (PFS) using iRECIST
Time frame: Within 24 months of last patient enrolled
Overall response (OS) using iRECIST
Time frame: Within 24 months of last patient enrolled
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Individual participant dataSharing planned: No
Related trials for Renal Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose Iglesias, MD study director
Consultant Chief Medical Officer for HiberCell, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HC-5404-FU in people with Renal Cell Carcinoma and Gastric Cancer, run by HiberCell, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of MTD of HC-5404-FU (time frame: Within 18 months of last patient enrolled). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.