VISORB: VISmodegib for ORbital and Periocular Basal Cell Carcinoma

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02436408
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Actual Duration (Months): 61.6
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Basal cell carcinoma (BCCA) is the most common human cancer, and frequently affects facial structures. While rarely fatal, facial BCCA can be disfiguring and expensive to treat.

Vismodegib is a small molecule inhibitor of SMO developed for the treatment of tumors in which the Hh signaling pathway appears to contribute to the development and maintenance of tumorigenesis. Vismodegib was recently approved by the Food and Drug Administration (FDA) for treatment of metastatic and locally advanced BCCA. Recent reports have suggested that vismodegib treatment for orbital BCCA may facilitate eye preservation even if surgery is eventually required

In order to assess the potential of vismodegib to improve the ophthalmic outcomes following treatment for orbital and/or periocular BCCA, this study will follow patients with globe-threatening orbital and lacrimal-threatening periocular BCCA who are being treated with vismodegib as standard of care.

Patients with tumors that do not respond to treatment with Vismodegib, and those who have a good response but poor tolerance of Vismodegib, will be offered surgical excision of the tumor. Patients with a good response and good tolerance of Vismodegib may continue the treatment as long as clinically indicated.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Basal Cell	Drug: Vismodegib	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: VISmodegib for ORbital and Periocular Basal Cell Carcinoma (VISORB)
• Actual Study Start Date: Jul 15, 2015
• Actual Primary Completion Date: Sep 1, 2020
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vismodegib 150mg taken orally once daily	Drug: Vismodegib

Outcome Measures

Primary Outcome Measures

1. The Number of Patients With a Score of 21 or Greater by the Visual Assessment Weighted Score (VAWS). [Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.]

   The VAWS was developed for the purpose of this study. It is made up of standard ophthalmic exam points, as well as subjective assessment of tearing and overall patient satisfaction. The maximum score is 50 and a score of 21 or greater will be considered a good outcome.

Secondary Outcome Measures

1. Number of Patients With Progressive Disease (PD) [Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.]

   Treatment response will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) protocol, using clinical measurements and/or tumor imaging measurements (determined by treating physician).

2. Number of Patients With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) AND Good Tolerance of Vismodegib [Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.]

   Tolerance will be self-reported by patient. Treatment response will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) protocol, using clinical measurements and/or tumor imaging measurements (determined by treating physician).

3. Number of Patients With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) AND Poor Tolerance of Vismodegib [Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.]

   Tolerance will be self-reported by patient. Treatment response will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) protocol, using clinical measurements and/or tumor imaging measurements (determined by treating physician).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients over 18 years of age with locally advanced or recurrent orbital or periorbital basal cell carcinoma (BCCA), or a medial canthal BCCA that threatens the lacrimal drainage system.

• Clinical assessment score obtained at baseline.

• Medical Oncology screening performed at baseline.

• Adequate BCCA size and location.

• Adequate hematopoietic capacity, hepatic and renal function.

• Male patients must agree to use condoms during treatment and for 3 months after last dose.

• Male patients must agree to not donate sperm during treatment and for 3 months after last dose.

• Participant must agree not to donate blood during the study and for 7 months after last dose.

• Informed consent signed.

• If the patient consents to enroll, then blood will be drawn and stored for biomarker analysis.

Exclusion Criteria:

• Inability or unwillingness to swallow capsules.

• Inability or unwillingness to comply with study procedures.

• Pregnant, lactating, or breast feeding women.

• Women of childbearing potential.

• Uncontrolled medical illness.

• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.

• Age under 18 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Cagri Besirli, M.D., Ph.D., University of Michigan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 11, 2020

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT02436408
• Other Study ID Numbers: UMCC 2014.022; HUM00082579
• First Posted: May 6, 2015
• Last Update Posted: Oct 28, 2021
• Last Verified: Sep 1, 2021

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Basal Cell

Study Results

Participant Flow

Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
Period Title: Overall Study
STARTED	35
COMPLETED	34
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
Overall Participants	35
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	17 48.6%
Male	18 51.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	34 97.1%
Unknown or Not Reported	1 2.9%
Region of Enrollment (participants) [Number]
United States	35 100%

Outcome Measures

1. Primary Outcome

Title	The Number of Patients With a Score of 21 or Greater by the Visual Assessment Weighted Score (VAWS).
Description	The VAWS was developed for the purpose of this study. It is made up of standard ophthalmic exam points, as well as subjective assessment of tearing and overall patient satisfaction. The maximum score is 50 and a score of 21 or greater will be considered a good outcome.
Time Frame	Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
Measure Participants	34
Count of Participants [Participants]	34 97.1%

2. Secondary Outcome

Title	Number of Patients With Progressive Disease (PD)
Description	Treatment response will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) protocol, using clinical measurements and/or tumor imaging measurements (determined by treating physician).
Time Frame	Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
Measure Participants	34
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Number of Patients With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) AND Good Tolerance of Vismodegib
Description	Tolerance will be self-reported by patient. Treatment response will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) protocol, using clinical measurements and/or tumor imaging measurements (determined by treating physician).
Time Frame	Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
Measure Participants	34
Count of Participants [Participants]	7 20%

4. Secondary Outcome

Title	Number of Patients With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) AND Poor Tolerance of Vismodegib
Description	Tolerance will be self-reported by patient. Treatment response will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) protocol, using clinical measurements and/or tumor imaging measurements (determined by treating physician).
Time Frame	Until end of study treatment (up to 15 months after start of study treatment); treatment duration ranged from 53 - 386 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
Measure Participants	34
Count of Participants [Participants]	27 77.1%

Adverse Events

Time Frame	Up to 15 months after start of study treatment; data was collected on study for 62 months total
Arm/Group Title	Vismodegib
Arm/Group Description	150mg taken orally once daily
All Cause Mortality
	Vismodegib
	Affected / at Risk (%)	# Events
Total	2/35 (5.7%)
Serious Adverse Events
	Vismodegib
	Affected / at Risk (%)	# Events
Total	9/35 (25.7%)
Cardiac disorders
Acute coronary syndrome	1/35 (2.9%)
Heart failure	1/35 (2.9%)
Gastrointestinal disorders
Colitis	1/35 (2.9%)
Gastrointestinal disorders - Other	1/35 (2.9%)
Nausea	2/35 (5.7%)
Vomiting	2/35 (5.7%)
Infections and infestations
Infections and infestations - Other	1/35 (2.9%)
Lung infection	2/35 (5.7%)
Sepsis	1/35 (2.9%)
Metabolism and nutrition disorders
Hypoglycemia	1/35 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1/35 (2.9%)
Renal and urinary disorders
Acute kidney injury	1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/35 (2.9%)
Pulmonary edema	1/35 (2.9%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other	1/35 (2.9%)
Vascular disorders
Vascular disorders - Other	1/35 (2.9%)
Other (Not Including Serious) Adverse Events
	Vismodegib
	Affected / at Risk (%)	# Events
Total	34/35 (97.1%)
Blood and lymphatic system disorders
Anemia	2/35 (5.7%)
Cardiac disorders
Sinus bradycardia	1/35 (2.9%)
Ear and labyrinth disorders
Hearing impaired	1/35 (2.9%)
Tinnitus	1/35 (2.9%)
Eye disorders
Blurred vision	1/35 (2.9%)
Cataract	2/35 (5.7%)
Dry eye	1/35 (2.9%)
Eye disorders - Other	8/35 (22.9%)
Eye pain	1/35 (2.9%)
Eyelid function disorder	3/35 (8.6%)
Watering eyes	3/35 (8.6%)
Gastrointestinal disorders
Abdominal pain	2/35 (5.7%)
Constipation	6/35 (17.1%)
Diarrhea	3/35 (8.6%)
Gastroesophageal reflux disease	5/35 (14.3%)
Nausea	11/35 (31.4%)
Vomiting	4/35 (11.4%)
General disorders
Chills	1/35 (2.9%)
Edema face	2/35 (5.7%)
Edema limbs	1/35 (2.9%)
Fatigue	12/35 (34.3%)
Fever	1/35 (2.9%)
General disorders and administration site conditions - Other	1/35 (2.9%)
Pain	4/35 (11.4%)
Infections and infestations
Papulopustular rash	2/35 (5.7%)
Injury, poisoning and procedural complications
Bruising	1/35 (2.9%)
Fall	2/35 (5.7%)
Investigations
Alanine aminotransferase increased	1/35 (2.9%)
Alkaline phosphatase increased	1/35 (2.9%)
Aspartate aminotransferase increased	1/35 (2.9%)
Creatinine increased	1/35 (2.9%)
Weight loss	12/35 (34.3%)
Metabolism and nutrition disorders
Anorexia	12/35 (34.3%)
Hyperglycemia	2/35 (5.7%)
Hyperkalemia	1/35 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/35 (8.6%)
Arthritis	2/35 (5.7%)
Back pain	4/35 (11.4%)
Generalized muscle weakness	5/35 (14.3%)
Muscle weakness lower limb	3/35 (8.6%)
Musculoskeletal and connective tissue disorder - Other	2/35 (5.7%)
Myalgia	23/35 (65.7%)
Pain in extremity	1/35 (2.9%)
Nervous system disorders
Dizziness	3/35 (8.6%)
Dysgeusia	26/35 (74.3%)
Facial muscle weakness	1/35 (2.9%)
Peripheral motor neuropathy	1/35 (2.9%)
Spasticity	7/35 (20%)
Psychiatric disorders
Agitation	1/35 (2.9%)
Hallucinations	1/35 (2.9%)
Insomnia	2/35 (5.7%)
Libido decreased	1/35 (2.9%)
Reproductive system and breast disorders
Erectile dysfunction	1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/35 (2.9%)
Epistaxis	1/35 (2.9%)
Nasal congestion	4/35 (11.4%)
Productive cough	1/35 (2.9%)
Sinus disorder	1/35 (2.9%)
Skin and subcutaneous tissue disorders
Alopecia	17/35 (48.6%)
Photosensitivity	1/35 (2.9%)
Pruritus	1/35 (2.9%)
Rash maculo-papular	1/35 (2.9%)
Skin and subcutaneous tissue disorders - Other	4/35 (11.4%)
Skin ulceration	2/35 (5.7%)
Urticaria	1/35 (2.9%)
Surgical and medical procedures
Surgical and medical procedures - Other	1/35 (2.9%)
Vascular disorders
Hypotension	1/35 (2.9%)

Limitations/Caveats

The initial study design aimed to enroll 50 patients; however, the study was terminated early as a consequence of the therapeutic and administrative challenges posed by the novel coronavirus pandemic and because the interim analysis revealed that the study at the point of termination was sufficient to achieve statistical significance.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.