NCT01898598

A Study of Vismodegib With Surgery in Participants With Previously Untreated Basal Cell Carcinoma

Terminated Phase 2 Results posted Last updated 8 May 2017

What this trial tests

Phase 2 trial testing Placebo in Basal Cell Carcinoma in 18 participants. Terminated before completion.

Timeline

23 January 2014

Primary endpoint
26 January 2016

26 January 2016

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	18
Start date	23 January 2014
Primary completion	26 January 2016
Estimated completion	26 January 2016
Sites	21 locations across United States

Drugs / interventions tested

• Placebo
• Vismodegib (vismodegib) — full drug profile →

Conditions studied

• Basal Cell Carcinoma — all drugs for Basal Cell Carcinoma →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Basal Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change in Target Basal Cell Carcinoma (BCC) Expected Surgical Defect Area at Mohs Micrographic Surgery (MMS) Visit Primary · Baseline, MMS visit (Week 12-14)

The percent change in target BCC expected surgical defect area was defined as (\[baseline expected surgical defect area - expected surgical defect area at MMS visit\]/ baseline expected surgical defect area) × 100 percent (%) where expected surgical defect area was manually outlined on a digital photograph and measured by a computer (computer aided planimetry). MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment.

Group	Value	95% CI
Vismodegib	31.52	± 35.580
Placebo	46.30	± 20.232

Actual Change in Target BCC Expected Surgical Defect Area at MMS Visit Secondary · Baseline, MSS Visit (Week 12-14)

Actual change was defined as (baseline expected surgical defect area - expected surgical defect area at MMS visit). MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment. Expected surgical defect area was manually outlined on a digital photograph and measured by a computer (computer aided planimetry).

Group	Value	95% CI
Vismodegib	70.16	± 82.483
Placebo	93.33	± 35.768

Percentage Change in Target BCC Actual Tumor-Free Margin Excision Area at MMS Visit Secondary · Baseline, MMS visit (Week 12-14)

Percent change in target BCC actual tumor-free margin excision area was defined as = (expected surgical defect area pre-treatment - actual tumor-free margin excision area at MMS visit) / expected surgical defect area pre-treatment) \* 100%. The actual tumor-free margin excision area (includes 2 millimeters \[mm\] margin) was measured during MMS. The area was photographed and traced on the digital photograph then calculated by computer-aided planimetry. MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment.

Group	Value	95% CI
Vismodegib	-12.24	± 78.775
Placebo	25.29	± 65.763

Percentage of Participants With Clinical Response Secondary · MMS visit (Week 12-14)

Clinical response was defined as a complete response (CR) or partial response (PR) at the post-treatment MMS excision. CR was defined as no histological evidence of BCC. PR was defined as a reduction of at least 50 % in the expected surgical defect area with histologic evidence of residual BCC. MMS visit was defined the visit that occurred within 2 weeks of the last study treatment.

Group	Value	95% CI
Vismodegib	18.2	2.3 – 51.8
Placebo	40.0	5.3 – 85.3

Percentage of Participants With Skip Area Secondary · MMS visit (Week 12-14)

Skip area was defined as the presence of non-contiguous residual tumor at the MMS visit, as determined by an independent dermatopathologist. MMS visit occurred within 2 weeks of the last study treatment.

Group	Value	95% CI
Vismodegib	0.0	0.0 – 28.5
Placebo	40.0	5.3 – 85.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 52 weeks after last study treatment (Last Study Treatment = Week 12). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vismodegib

Serious: 3/11 (27%)

Deaths: —

Placebo

Serious: 0/5 (0%)

Deaths: —

Serious adverse events (4 terms)

Reaction	System	Vismodegib	Placebo
Gastric ulcer	Gastrointestinal disorders	—	—
Oesophagitis	Gastrointestinal disorders	—	—
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Other adverse events (22 terms — click to expand)

Reaction	System	Vismodegib	Placebo
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Influenza like illness	General disorders	—	—
Bronchitis	Infections and infestations	—	—
Laceration	Injury, poisoning and procedural complications	—	—
Fall	Injury, poisoning and procedural complications	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Ageusia	Nervous system disorders	—	—
Nerve compression	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Confusional state	Psychiatric disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Sinus congestion	Respiratory, thoracic and mediastinal disorders	—	—
Skin ulcer	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—

Most-reported serious reactions: Gastric ulcer, Oesophagitis, Bladder neoplasm, Malignant melanoma.

Data from ClinicalTrials.gov NCT01898598 adverse events section.

Sponsor's own description

This randomized, double-blind, placebo-controlled study will assess the efficacy and safety of vismodegib with surgery in participants with basal cell carcinoma.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.
   Rimkus TK, Carpenter RL, Qasem S, Chan M, et al · · 2016 · cited 411× · PMID 26891329 · DOI 10.3390/cancers8020022
2. Hedgehog Signaling: From Basic Biology to Cancer Therapy.
   Wu F, Zhang Y, Sun B, McMahon AP, et al · · 2017 · cited 243× · PMID 28286127 · DOI 10.1016/j.chembiol.2017.02.010
3. Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells.
   Sari IN, Phi LTH, Jun N, Wijaya YT, et al · · 2018 · cited 155× · PMID 30423843 · DOI 10.3390/cells7110208
4. Strategies for modern biomarker and drug development in oncology.
   Smith AD, Roda D, Yap TA. · · 2014 · cited 89× · PMID 25277503 · DOI 10.1186/s13045-014-0070-8
5. Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance.
   Nguyen NM, Cho J. · · 2022 · cited 88× · PMID 35163655 · DOI 10.3390/ijms23031733
6. The role of Hedgehog and Notch signaling pathway in cancer.
   Xia R, Xu M, Yang J, Ma X. · · 2022 · cited 39× · PMID 36517618 · DOI 10.1186/s43556-022-00099-8
7. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options - role of smoothened inhibitors.
   Fecher LA, Sharfman WH. · · 2015 · cited 23× · PMID 26604681 · DOI 10.2147/btt.s54179