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.
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
Interventions
Drug | Synonyms | Arms |
---|
SM08502 | | Cohort 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
Name | Type | Description | Interventions |
---|
Cohort 1 | Experimental | SM08502 10 mg | |
Cohort 2 | Experimental | SM08502 20 mg | |
Cohort 3 | Experimental | SM08502 40 mg | |
Cohort 4 | Experimental | SM08502 60 mg | |
Cohort 5 | Experimental | SM08502 80 mg | |
Cohort 6 | Experimental | SM08502 120 mg | |
Cohort 7 | Experimental | SM08502 160 mg | |
Cohort 8 | Experimental | SM08502 200 mg | |
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