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A Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors

NCT03355066

Description:

This study is an open-label, multi-center, dose-escalation study in adult subjects with advanced solid tumors for whom standard therapy is not available for their stage of disease. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics (preliminary anti-tumor activity and gene expression analysis) of SM08502 administered orally, once daily, for 28 consecutive days. Dosing in 28-day cycles will continue within each subject, unless treatment is discontinued due to toxicity, disease progression, initiation of a new anti-neoplastic therapy, withdrawal of consent, the Sponsor terminates the study, or the subject no longer meets retreatment criteria.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Dose-Escalation, Dose-Finding Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SM08502-ONC-01
  • NCT ID: NCT03355066

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
SM08502Cohort 1

Purpose

This study is an open-label, multi-center, dose-escalation study in adult subjects with advanced solid tumors for whom standard therapy is not available for their stage of disease. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics (preliminary anti-tumor activity and gene expression analysis) of SM08502 administered orally, once daily, for 28 consecutive days. Dosing in 28-day cycles will continue within each subject, unless treatment is discontinued due to toxicity, disease progression, initiation of a new anti-neoplastic therapy, withdrawal of consent, the Sponsor terminates the study, or the subject no longer meets retreatment criteria.

Detailed Description

      Cohorts of subjects with advanced solid tumors will receive increasing doses of SM08502 at
      fixed daily doses of 10, 20, 40, 60, 80, 120, 160, or 200 mg. If the maximum tolerated dose
      (MTD) is not determined at the 200 mg dose, dosing will continue at 50 mg/dose increments
      until an MTD is determined.

      Cohorts will include approximately 1 to 6 subjects according to an accelerated escalation
      design and safety requirements for expansion of subject numbers.

      For the purpose of dose escalation and de-escalation, the dose of the study drug and regimen
      may be modified based on the type of dose limiting toxicities (DLTs) observed and following
      data review and discussions between the Sponsor and Investigators.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalSM08502 10 mg
  • SM08502
Cohort 2ExperimentalSM08502 20 mg
  • SM08502
Cohort 3ExperimentalSM08502 40 mg
  • SM08502
Cohort 4ExperimentalSM08502 60 mg
  • SM08502
Cohort 5ExperimentalSM08502 80 mg
  • SM08502
Cohort 6ExperimentalSM08502 120 mg
  • SM08502
Cohort 7ExperimentalSM08502 160 mg
  • SM08502
Cohort 8ExperimentalSM08502 200 mg
  • SM08502

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects with advanced solid tumors who are refractory to or intolerant of established
             therapy known to provide clinical benefit for their condition (i.e., subjects must not
             be candidates for regimens known to provide clinical benefit).

          -  Measurable or evaluable disease

          -  Subjects must have recovered from all toxicity associated with previous chemotherapy,
             targeted therapy, experimental therapy, biological therapy, immuno-oncology therapy,
             surgery, radiotherapy, or other locoregional therapy. (Exception: Subjects may enter
             with continuing alopecia.) The following intervals must elapse between end of last
             treatment and receiving the first dose of SM08502:

               1. Chemotherapy: 3 weeks

               2. Mitomycin C or a nitrosourea: 6 weeks

               3. Radiotherapy: 6 weeks

               4. Major surgery: 6 weeks

               5. Targeted therapy, including monoclonal antibodies and immuno-oncology therapies:
                  4 weeks or 5 half-lives, whichever is shortest

               6. Hormonal therapy: 4 weeks or 5 half-lives, whichever is shortest

               7. Experimental therapy: 4 weeks or 5 half-lives, whichever is shortest

               8. Other locoregional therapy [e.g., radiofrequency ablation (RFA), TACE
                  (transarterial chemoembolization), TARE (transarterial radioembolization),
                  DEB-TACE (drug eluting bead transarterial chemoembolization)]: 6 weeks

          -  Life expectancy > 3 months

          -  Subjects must have no uncontrolled intercurrent illness

          -  Subjects must have the ability to swallow and retain oral medication

          -  Subjects must be willing to avoid extensive sun exposure, phototherapy, and use of a
             tanning salon during trial participation.

          -  Subjects must be willing to sign and provide informed consent and be capable of giving
             informed consent in accordance with the Institutional Review Board/Ethics Committee
             policy

        Exclusion Criteria:

          -  Women who are pregnant or lactating

          -  Women of childbearing potential who are sexually active and are not willing to use a
             highly effective method of birth control during the study period

          -  Males who are sexually active and not willing to use a condom, and have a partner who
             is capable of becoming pregnant, if neither has had surgery to become sterilized,
             and/or who are not willing to use double barrier or whose partner is not using a
             highly effective method of birth control

          -  Subjects with myocardial infarction (heart attack) within 1 year

          -  Subjects using agents known to inhibit or induce CYP3A4, such as ketoconazole,
             itraconazole, erythromycin, or rifampin, within 7 days prior to study start

          -  Subjects with active infection requiring antibiotic therapy

          -  Organ transplant recipients

          -  Subjects with brain metastasis

          -  Subjects with history of osteoporosis

          -  Subjects with known active human immunodeficiency virus, hepatitis B virus, or
             hepatitis C virus infection

          -  Subjects with any retinal abnormalities, including subjects with diabetic retinopathy,
             macular degeneration, or other known forms of retinal degenerative disease

          -  Subjects with chronic liver disease or dysfunction
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability: treatment-emergent adverse events (TEAEs)
Time Frame:Cycle 6, Day 29 (approximately Day 180)
Safety Issue:
Description:Evaluate the safety and tolerability of SM08502 as measured by TEAEs during the entire treatment period

Secondary Outcome Measures

Measure:Tumor response
Time Frame:Cycle 3, Day 1 (approximately Day 60); Cycle 5, Day 1 (approximately Day 120); Cycle 6, Day 29 (approximately Day 180)
Safety Issue:
Description:Evaluate change from baseline in tumor characteristics as measured by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Samumed LLC

Trial Keywords

  • Wnt pathway
  • Wnt inhibition
  • SM08502

Last Updated

January 20, 2021