This phase 2, open label, dose escalation study is designed to evaluate the safety,
tolerability and efficacy of various doses of STP705 administered as localized injection in
patients with Basal Cell Carcinoma (BCC).
Goals:
- To determine the safe and effective recommended dose of STP705 for the treatment of
basal cell carcinoma.
- Analysis of biomarkers common to BCC formation pathway including TGF-β1 and COX-2.
Basal cell carcinoma occurs most often on areas of the skin that are exposed to the sun, such
as head and neck. The most commonly found clinical feature of Basal Cell Carcinoma (BCC) is
an elevated tumor with a pearly and translucent margin and telangiectasia. The color may vary
widely from nearly normal skin color to erythematous to violaceous and may also be pigmented.
BCC may also resemble noncancerous skin conditions such as eczema or psoriasis. The majority
of these cancers occur on areas of skin that are regularly exposed to sunlight or other
ultraviolet radiation.
The STP705 drug substance (STP705) is composed of two siRNA oligonucleotides, targeting the
expression of TGF-β1 and Cox-2 mRNA respectively. Along with the HKP-enhanced delivery
system, the combination is expected to downregulate TGF-β1 and COX-2 expression resulting in
the inhibition of tumor growth and provide an alternative non-invasive approach for the
treatment of BCC.
This phase 2, open label, dose escalation study is designed to evaluate the safety,
tolerability and efficacy of various doses of STP705 administered as localized injection in
patients with BCC. This study seeks to establish a safe and effective recommended dose of
STP705 for the treatment of BCC. The clinician will evaluate the change in tumor size at each
treatment visit. At the End of Treatment visit, the residual tumor, or former tumor location,
will be excised for analysis. Expression of biomarkers common to the BCC formation pathway,
including TGF-β1 and COX-2, will be evaluated.
Safety and tolerability will be assessed by the number of incidence of adverse events (AEs)
and serious adverse events (SAEs); the incidence of AEs and SAEs leading to discontinuation
of trial medication; the incidence and severity of Local Skin Response (LSR);
hypopigmentation and hyperpigmentation following treatment; and the tolerability of repeated
localized administration of STP705 as assessed by investigator-evaluation of injection site
reactions for all patients and within each cohort.
The study plans to enroll approximately 15 adult patients at up to 3 clinical sites in the
United States. The 15 patients will be divided equally among 3 cohorts (30, 60 and 90 μg dose
level) of 5 patients each.
Inclusion Criteria: Subjects are required to meet all of the following criteria for
enrollment into the study:
1. Male or female adult ≥ 18 years of age.
2. Primary, histologically confirmed trunk or extremity
(non-peri-orbital/-anogenital/-facial/-scalp) basal cell carcinoma lesion suitable for
excision with a minimum diameter of 0.5 cm and with a maximum diameter of 2.0 cm.
3. Histological diagnosis made no more than 6 months prior to the screening visit.
4. Histological biopsy removed ≤25% of the original volume of the target lesion.
5. No other dermatological disease in the BCC target site or surrounding area, which in
the opinion of the investigator, could interfere with the study.
6. Willing to refrain from using non-approved lotions or creams on the target site and
surrounding area during the treatment period.
7. Willing to refrain from exposure to excessive direct sunlight or ultraviolet light and
to avoid the use of tanning parlors for the duration of the study.
8. Laboratory values for the tests (listed in the Study Schedule) within the reference
ranges as defined by the central laboratory, or "out of range" test results that is
clinically acceptable to the investigator. Ability to follow study instructions and
likely to complete all study requirements.
9. Written informed consent obtained, including consent for tissue to be examined and
stored by the Central Histology Lab.
10. Written consent to allow photographs of the target BCC lesion to be used as part of
the study data and documentation.
11. For females of childbearing potential, a negative pregnancy test at screening and
using an acceptable form of birth control (oral / implant/ injectable/ transdermal
contraceptives, intrauterine device, condom, diaphragm, abstinence, or a monogamous
relationship with a partner who has had a vasectomy).
Exclusion Criteria:
1. Pregnant or lactating.
2. Presence of known or suspected systemic cancer.
3. Histological evidence of SCC, or any other non-BCC tumor in the biopsy specimen.
4. Histological evidence of infiltrative or other aggressive histological subtype growth
patterns in the biopsy specimen.
5. History of recurrence of the target BCC lesion.
6. Evidence of dermatological disease or confounding skin condition with in 2 cm margin
of the target BCC lesion, e.g., SCC, actinic keratosis, rosacea, psoriasis, atopic
dermatitis, eczema, xeroderma pigmentosa.
7. Concurrent disease or treatment that suppresses the immune system;
8. Patients with baseline QTC > 480 msec using Frederica's formula.
9. Chronic medical condition that in the judgment of the investigator(s) would interfere
with the performance of the study or would place the patient at undue risk.
10. Known sensitivity to any of the ingredients in the study medication.
11. Use of a tanning beds or other excessive or prolonged exposure to ultraviolet light or
direct sunlight during the study.
12. Treatment with systemic chemotherapeutic agents within the 6 months prior to the
screening visit.
13. Use of systemic retinoids within the 6 months prior to the screening period.
14. Treatment with systemic immunomodulators or immunosuppressants within the 6 months
prior to the screening period.
15. Use of topical immunomodulators within 2 cm of the target BCC lesion within the 4
weeks prior to the screening period.
16. Treatment with the following topical agents within 2 cm of the target BCC lesion
within the 4 weeks prior to the screening visit: amino-levulinic acid, 5-fluorouracil,
corticosteroids, retinoids, diclofenac, ingenol mebutate, or imiquimod.
17. Treatment with liquid nitrogen, surgical excision (excluding diagnostic incisional
biopsy) or curettage within 2 cm of the target BCC lesion during the 4 weeks prior to
the screening visit.
18. Evidence of current chronic alcohol or drug abuse.
19. Current enrollment in an investigational drug or device study or participation in such
a study within 4 weeks of the screening visit.
20. In the investigator's opinion, evidence of unwillingness, or inability to follow the
restrictions and requirements of the protocol and complete the study.
21. Taking any other investigational product within 1 month of first dose of STP705.
