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Safety, Tolerability, and Pharmacokinetics of CAL056 Mesylate in Patients With Resistant or Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT04686383
Recruitment Status : Recruiting
First Posted : December 28, 2020
Last Update Posted : June 11, 2021
Sponsor:
Information provided by (Responsible Party):
Calgent Biotechnology Co., Ltd

Brief Summary:
This is a multi-center, open-label, dose-escalation, phase I study to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary efficacy, and pharmacodynamics of CAL056 mesylate in cancer patients with resistant or refractory solid tumors.

Condition or disease Intervention/treatment Phase
Resistant or Refractory Solid Tumors Drug: CAL056 mesylate Phase 1

Detailed Description:

Patients with resistant or refractory malignant solid tumors and no standard treatment available will be screened for the eligibility. Patients will be screened within 28 days prior to the first dose of CAL056 mesylate. Eligible patients will receive CAL056 mesylate daily with the assigned dose level for 28 days (Day 1 to Day 28) for each treatment cycle. Patients will be administered with CAL056 mesylate at clinical site at scheduled visits (i.e. Day 1/Visit 1, Day 8/Visit 2, Day 15/ Visit 3, Day 22/Visit 4, Day 28/Visit 5). Remaining doses of CAL056 mesylate on all other days will be self-administered by patients at home. After the administration of CAL056 mesylate on Day 1 and Day 28, patients can stay at the clinical site for 24 hours to have safety monitoring and blood samples collected for PK analysis.

Only patients completing Cycle 1 without a dose-limiting toxicity (DLT) or disease progression will be allowed to continue the subsequent cycles at the same dose level. The maximum number of dosing cycle is 6 cycles in each patient in this study. Continuation of using CAL056 mesylate may be permitted after the evaluation of the risk/benefit in individual patient by the Investigators and with the approval of Calgent.

During the Cycle 1 of study period, a total of 5 visits are scheduled to evaluate the safety, PK, preliminary efficacy, and pharmacodynamics of CAL056 mesylate. Each visit is planned on Day 1 of each subsequent cycle if patients continue the treatment of CAL056 mesylate. After the end treatment of CAL056 mesylate, an end of treatment (EOT) visit and a safety follow-up visit will be scheduled.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multi-center, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CAL056 Mesylate in Patients With Solid Tumors Resistant or Refractory to Standard Treatments
Actual Study Start Date : December 29, 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Arm Intervention/treatment
Experimental: Cohort 1: 20 mg CAL056 mesylate
Patients will receive oral dose of 20 mg CAL056 mesylate once daily under fasting condition in the morning for 28 days during each cycle.
Drug: CAL056 mesylate
Dosage form: 20 mg CAL056 mesylate/tablet

Experimental: Cohort 2: 40 mg CAL056 mesylate
Patients will receive oral dose of 40 mg CAL056 mesylate once daily under fasting condition in the morning for 28 days during each cycle.
Drug: CAL056 mesylate
Dosage form: 20 mg CAL056 mesylate/tablet

Experimental: Cohort 3: 80 mg CAL056 mesylate
Patients will receive oral dose of 80 mg CAL056 mesylate once daily under fasting condition in the morning for 28 days during each cycle.
Drug: CAL056 mesylate
Dosage form: 20 mg CAL056 mesylate/tablet

Experimental: Cohort 4: 120 mg CAL056 mesylate
Patients will receive oral dose of 120 mg CAL056 mesylate once daily under fasting condition in the morning for 28 days during each cycle.
Drug: CAL056 mesylate
Dosage form: 20 mg CAL056 mesylate/tablet

Experimental: Cohort 5: 160 mg CAL056 mesylate
Patients will receive oral dose of 160 mg CAL056 mesylate once daily under fasting condition in the morning for 28 days during each cycle.
Drug: CAL056 mesylate
Dosage form: 20 mg CAL056 mesylate/tablet




Primary Outcome Measures :
  1. Number of patients with adverse events (AEs), serious adverse events (SAEs), and treatment emergent adverse events (TEAEs) [ Time Frame: From screening visit until safety follow-up visit (at 28 days after the EOT) or before starting new anticancer treatment, whichever comes first (up to 1-year) ]
    To evaluate the safety and tolerability of CAL056 mesylate in cancer patients.

  2. Number of patients with AEs qualified as dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (28 days) ]
    Dose-limiting toxicities are evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  3. Determination of tolerability and maximum tolerated dose (MTD) of CAL056 mesylate by DLTs using NCI CTCAE version 5.0 [ Time Frame: Cycle 1 (28 days) ]
    MTD will be the highest dose associated with occurrence of DLTs ≤ 33% (e.g. 2/6 evaluable patients experience a DLT during the first treatment Cycle).

  4. Evaluation of the PK profile of CAL056 mesylate: Maximum observed concentration (Cmax) [ Time Frame: At Day 1 and Day 28 of Cycle 1, at Day 1 of subsequent cycles until Cycle 6 (except for Cycle 2) (each cycle is 28 days in length) ]
    Pharmacokinetics profile will be evaluated following a comprehensive PK parameter, such as Cmax.

  5. Evaluation of the PK profile of CAL056 mesylate: Time to reach Cmax (Tmax) [ Time Frame: At Day 1 and Day 28 of Cycle 1, at Day 1 of subsequent cycles until Cycle 6 (except for Cycle 2) (each cycle is 28 days in length) ]
    Pharmacokinetics profile will be evaluated following comprehensive PK parameter, such as Tmax.

  6. Evaluation of the PK profile of CAL056 mesylate: Apparent terminal elimination half-life (t½) [ Time Frame: At Day 1 and Day 28 of Cycle 1, at Day 1 of subsequent cycles until Cycle 6 (except for Cycle 2) (each cycle is 28 days in length) ]
    Pharmacokinetics profile will be evaluated following comprehensive PK parameter, such as t½.

  7. Evaluation of the PK profile of CAL056 mesylate: Area under the concentration-time curve (AUC) [ Time Frame: At Day 1 and Day 28 of Cycle 1, at Day 1 of subsequent cycles until Cycle 6 (except for Cycle 2) (each cycle is 28 days in length) ]
    Pharmacokinetics profile will be evaluated following a comprehensive PK parameter, AUC.

  8. Preliminary determination of the recommended phase II dose (RP2D) of CAL056 mesylate [ Time Frame: Cycle 1 (28 days) ]
    The RP2D will be preliminarily determined by the PK profile, type and severity of drug related toxicity, clinical suitability for long-term administration.


Secondary Outcome Measures :
  1. Evaluation of the preliminary efficacy of CAL056 mesylate in tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: At the screening visit and within 7 days prior to Day 1 of odd cycles (i.e., Cycle 3 and Cycle 5) (each cycle is 28 days in length) and at EOT/Early Termination (ET) (up to 21 months) ]
    Tumor response will be assessed by RECIST version 1.1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with age ≥ 18 years old
  • Patients with resistant or refractory solid tumors confirmed by histology which are unresponsive to standard therapies
  • Patients with at least one measurable lesion per RECIST version 1.1.
  • Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤ 2
  • Patients with at least 3 months of life expectancy as judged by the investigators
  • Patients with adequate bone marrow reserve and organ function
  • Patients with the negative result for testing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
  • Female patients are eligible to participate if they are of non-childbearing potential or have documentation of a negative serum pregnancy test at screening. Sexually active pre-menopausal women of childbearing potential must agree to use adequate, highly effective contraceptive measures during and upon completion of the study and for at least 6 months after the last dose of study drug
  • Male patients who agree to use an adequate method of contraception during and upon completion of the study and for at least 6 months after the last dose of study drug
  • Patients must be willing and be able to provide written informed consent for the study.

Exclusion Criteria:

  • History of other invasive malignancy that is currently active and/or has been treated within 12 months prior to screening
  • Patients with the presence of symptomatic central nervous system (CNS) metastases requiring radiation treatment, surgery, or continuous use of corticosteroids or patients with untreated or developing brain metastasis causing any symptoms, such as neurologic deficits, seizures, or headache
  • Any prior adjuvant cytotoxic chemotherapy within 4 weeks prior to screening
  • Any radiotherapy within 2 weeks prior to screening
  • Pre-existing chemotherapy-related peripheral neuropathy
  • Currently participating or has participated in a study of an investigational product within 4 weeks prior to the first dose of CAL056 mesylate
  • Patients with history of organ or stem cell transplant requiring immunosuppressive medications
  • Active autoimmune disease
  • Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis
  • Patients who have chronic obstructive pulmonary disease (COPD) or asthma
  • Has a history of pneumonitis that required steroids or current pneumonitis
  • Known significant liver disease
  • Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies)
  • Has received live attenuated vaccination within 30 days prior to the first dose of CAL056 mesylate
  • Female patients who is pregnant, breast-feeding, or planning to become pregnant
  • Patients with corrected QT interval (QTc) interval of > 450 msec.
  • Has history of clinically significant or severe gastrointestinal disease or condition that may affect drug absorption within the past 3 months.

Information from the National Library of Medicine

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): NCT04686383


Contacts
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Contact: Irene Tsai +886 2 2732 2782 ext 121 irenetsai@calgent.com
Contact: Judith Hou judith_hou@calgent.com

Locations
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United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, M.D.         
United States, Texas
NEXT Oncology, 2829 Babcock Road Suite 300 Recruiting
San Antonio, Texas, United States, 78229
Contact: Anthony W. Tolcher, M.D.         
Taiwan
Tzu Chi General Hospital, Taipei Branch Recruiting
New Taipei City, Taiwan
Contact: Her-Shyong Shiah, M.D.         
Sponsors and Collaborators
Calgent Biotechnology Co., Ltd
Investigators
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Study Chair: Yun Yen, M.D. Calgent Biotechnology Co., Ltd
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Responsible Party: Calgent Biotechnology Co., Ltd
ClinicalTrials.gov Identifier: NCT04686383    
Other Study ID Numbers: CAL056-101
First Posted: December 28, 2020    Key Record Dates
Last Update Posted: June 11, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Calgent Biotechnology Co., Ltd:
CAL056 mesylate
Oncology
Dose-limiting toxicity
Maximum tolerated dose
Pharmacokinetics
Safety
Additional relevant MeSH terms:
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Neoplasms