Phase II Study of Radiation Therapy and Vismodegib for Advanced Head/Neck Basal Cell Carcinoma

• Sponsor: Sue Yom (Other)
• Overall Status: Completed
• CT.gov ID: NCT01835626
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 24
• Locations: 2
• Arm: 1
• Duration (Months): 76.3
• Patients Per Site: 12
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Chemotherapy, radiation therapy, and surgery are standard treatments for basal cell carcinoma at most institutions. The purpose of this study is to determine whether adding vismodegib to radiation (chemoradiotherapy) is safe and tolerable. The purpose of this study is to assess the safety and tolerability of combined radiation therapy and vismodegib. This combination may increase the chances of the tumors being destroyed or unable to spread to other parts of the body in people with locally advanced basal cell carcinoma of the head and neck.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Basal Cell Carcinoma; Skin Cancer; Cutaneous Malignancy	Drug: Vismodegib; Radiation: Radiation therapy	Phase 2

Detailed Description

This is a single arm, multi-center Phase II clinical trial to assess the safety and demonstrate the efficacy of a combined modality approach using radiation therapy after induction and concurrently with systemic administration of vismodegib, which may increase the rates of complete response and sustained local control in patients with locally advanced Basal Cell Carcinoma (BCC)

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Radiation Therapy and Vismodegib, for the Treatment of Locally Advanced Basal Cell Carcinoma of the Head and Neck
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Sep 10, 2019
• Actual Study Completion Date: Sep 10, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Vismodegib and Radiation Therapy 150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes.

Drug: Vismodegib; Vismodegib will be taken daily for 12 weeks. It should be taken at approximately the same time each day. Patients will be given a supply of vismodegib on Week 1, Day 1 to last until their next study visit. They will be asked to keep a record of each dose of vismodegib you take. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.; Other Names: Erivedge ; Radiation: Radiation therapy; Radiation therapy will be started after the patient has finished taking vismodegib for 12 weeks. They will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Local-regional Control Rate [Up to 12 months after completing therapy]

   The local-regional control rate at 12 months from protocol therapy completion, defined as absence of progressive disease within the irradiated planning tumor volumes (PTV) for patients with locally advanced basal cell carcinoma in the head and neck.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [From treatment start up to 12 months after completing therapy]

   Estimate of the probability of PFS, with failure defined as any disease recurrence or death due to any cause with each duration measured from the time of first treatment with vismodegib to 12 months after completion of study treatment

2. Overall Survival (OS) [From treatment start up to 12 months after completing therapy]

   Estimate of the probability of OS, with failure defined as any disease recurrence or death due to any cause with each duration measured from the time of first treatment with vismodegib to 12 months after completion of study treatment

3. Percentage of Patients by Treatment-Related Adverse Events by Event Description [up to 12 months after completing therapy]

   The percentage of any adverse events (CTCAE, v. 4.0) assessed to be definitely, probably, or possibly related to vismodegib or its combination with radiation therapy at any point during protocol therapy or during the followup period.

4. Percentage of Patients by Adverse Event Not Related to Disease Progression [up to 12 months after completing therapy]

   The percentage of patients experiencing Grade 4-5 adverse events classified using CTCAE v.4.1 assessed to be definitely, probably, or possibly related to the induction or concurrent treatment components of the protocol regimen (that is not definitely related to disease progression) at any point during protocol therapy or during the followup period

5. Number of Patients Discontinuing Treatment Due to Toxicity [up to 6 months from treatment start]

   Feasibility of administering concurrent vismodegib with radiation therapy was assessed by the number of patients discontinuing treatment due to toxicity during the concurrent administration of vismodegib and radiation therapy (<75% of planned radiation therapy delivered)

6. Clinical Response Rate [Up to 12 months after completing therapy]

   Response rate (as per RECIST) of the primary site and regionally involved areas following all treatment components at 3 months after the completion of protocol therapy will be reported as a percentage of the total sample.

7. Percentage of Patients With a Decrease of Basal Cell Carcinoma (BCC) [Up to 12 months after completing therapy]

   Proportion of patients with a decrease of BCC within the irradiated planning tumor volumes (PTV) in patients who complete initial combined therapy, indicating a clinical response to vismodegib and radiation therapy

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients with locally advanced BCC of the head and neck, consisting of at least one histologically or cytologically confirmed lesion greater than or equal to 20 mm in longest diameter that is considered to be inoperable or to have a medical contraindication to surgery, in the opinion of a Mohs dermatologic surgeon, head and neck surgeon, or plastic surgeon. Locally advanced disease is considered to include involved lymph nodes of the neck. A patient with regionally involved lymph nodes in the neck is considered eligible. The patient should be considered a candidate for radiotherapy and should not have medical contraindications to receipt of radiation therapy.

If a patient has distant metastatic spread of BCC (e.g., spread to distant areas outside the regional lymph nodes, clearly non contiguous areas of bone involvement, or distant metastasis to lung, brain, or other visceral organs), the patient should be considered as having distant metastasis and is not eligible.

Note: All lesions that the investigator proposes to follow as target lesions during the course of the study must have previously been histologically confirmed as BCC.

Acceptable contraindications to surgery include:

• BCC that has recurred in the same location after two or more surgical procedures and successful curative resection is deemed unlikely

• Complete surgical resection is not possible or is deemed excessively morbid (e.g. invasion into cranial nerves or skull base, proximity to brain, spinal canal, or orbit)

• Anticipated substantial morbidity and/or major deformity from surgery (e.g. removal of a major facial structure, such as nose, ear, eyelid, eye, or jaw; or requirement for upper limb amputation)

• Medical contraindication to surgery

• Patient refusal of surgery due to anticipated morbidity

• Other conditions considered to be contraindicating must be discussed with Data Coordinator before enrolling the patient.

1. Prior radiation therapy is acceptable but there cannot be major overlap of the previously irradiated tissues with the new radiation treatment volumes anticipated to be delivered for the purposes of this protocol, in such a way that curative intent with radiation cannot be met. Furthermore, the total dose from all radiation delivered and expected to be delivered should not exceed the suggested dose constraints given for normal structures.

2. Zubrod Performance Status 0-2

3. Age of greater than or equal to 18 years

4. Adequate bone marrow and organ function defined as follows:

Adequate bone marrow function:

leukocytes:> 3,000/microliter (mcL) absolute neutrophil count: greater than or equal to 1000 cells/mm3 platelets: greater than or equal to 75,000 cells/mm3 hemoglobin: greater than or equal to 8.5 g/dl (recommended cutoff subject to judgment of medical oncologist), but cannot be transfusion dependent

Adequate hepatic function:

total bilirubin: less than or equal to 1.5x institutional upper limit of normal (ULN) or within 3x the ULN for patients with Gilbert disease aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) : < 3 X institutional upper limit of normal alanine aminotransferase (ALT) /serum glutamic-pyruvic transaminase (SGPT): < 3 X institutional upper limit of normal

Adequate renal function:

creatinine: within normal institutional limits OR creatinine clearance: > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

1. Agreement not to donate blood or blood products during the study and for 7 months after discontinuation of vismodegib; for male patients, agreement not to donate sperm during the study and for 7 months after discontinuation of vismodegib.

2. For male patients, agreement not to donate sperm during the study and for 3 months after the final dose of vismodegib. Male patients must use condoms at all times, even after a vasectomy, during sexual intercourse with pregnant partners or female partners of reproductive potential during treatment with vismodegib. Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm.

3. Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating vismodegib. For women of childbearing potential, a negative pregnancy test within 7 days prior to commencement of dosing is required. Women of reproductive potential are required to use two forms of acceptable contraception (including one acceptable barrier method with spermicide) during therapy and for 7 months after completing therapy. Acceptable forms of primary contraception include the following: Combination hormonal contraceptives, subcutaneous hormonal implant, hormonal patch, hormonal contraceptives (levonorgestre-releasing intrauterine system, medroxyprogesterone acetate depot), tubal sterilization, vasectomy, and intrauterine device (IUD). Acceptable forms of barrier contraception include the following: any male condom (with spermicide) or diaphragm (with spermicide).

Exclusion Criteria:

1. Patients with distant metastasis (e.g. spread to distant areas outside the regional lymph nodes, clearly non contiguous areas of bone involvement, or distant metastasis to lung, brain, liver or other visceral organs) are ineligible.

2. Patients with nevoid BCC syndrome (Gorlin syndrome) should not enroll in this study.

3. A patient with a known other malignancy is eligible if there is a negligible risk for disease progression or death within one year, there is no active ongoing treatment for this malignancy, and the malignancy and/or any anticipated future treatments would not interfere with protocol-mandated evaluations at 1 year.

4. Prior vismodegib or other antagonists of the Hh pathway;

5. Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy, topical therapy such as 5-Fluorouracil or imiquimod, radiation therapy, surgery, or photodynamic therapy.

• For patients with multiple cutaneous BCCs at baseline that are not designated by the investigator as target lesions, treatment of these non-target BCCs with surgery may be permitted but must be discussed with Data Coordinator prior to any surgical procedure.

1. Recent (within 4 weeks of Registration), current, or planned participation in another experimental drug study.

2. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields in such a way that curative intent with radiation cannot be met

3. Inability or unwillingness to swallow capsules; Patients with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:

• any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills;

• prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel;

• active peptic ulcer disease;

• malabsorption syndrome

1. Pregnant or lactating women. Patients who are unable or are unwilling to adhere to the required contraceptive methods are excluded from the study.

• Women of reproductive potential are required to use two forms of acceptable contraception (including one acceptable barrier method with spermicide) during therapy and for 7 months after completing therapy. Acceptable forms of primary contraception include the following: Combination hormonal contraceptives, subcutaneous hormonal implant, hormonal patch, hormonal contraceptives (levonorgestre-releasing intrauterine system, medroxyprogesterone acetate depot), tubal sterilisation, vasectomy and intrauterine device (IUD). Acceptable forms of barrier contraception include the following: Any male condom (with spermicide) or diaphragm (with spermicide).

• Male patients must use condoms at all times, even after a vasectomy, during sexual intercourse with female partners of reproductive potential during treatment with vismodegib and for 2 months after the last dose to avoid exposing a pregnant partner and unborn fetus to vismodegib.

1. Life expectancy of <1 year

2. Patients with widespread superficial multifocal BCC who are considered unresectable due to breadth of involvement and do not have a single definable area of disease amenable to radiation therapy targeting.

Note: If an area including one or more lesions is definable for radiation therapy targeting, the patient may be eligible for treatment on study using the designated target lesion(s) identified by the investigator.

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements;

2. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk form treatment complications

3. HIV-positive patients on combination antiretroviral therapy, because of the potential for pharmacokinetic interactions with vismodegib;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94115
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Sue Yom
• Genentech, Inc.

Investigators

• Principal Investigator: Sue Yom, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 7, 2016
• Informed Consent Form - Feb 8, 2018

More Information

Publications

None provided.

• Responsible Party: Sue Yom, Associate Professor, Department of Radiation Oncology, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01835626
• Other Study ID Numbers: 122011; NCI-2013-00871
• First Posted: Apr 19, 2013
• Last Update Posted: May 3, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sue Yom, Associate Professor, Department of Radiation Oncology, University of California, San Francisco: Locally advanced basal cell carcinoma; Skin cancer; Radiation therapy; Vismodegib; Head and neck cancer; Cutaneous malignancy
• Additional relevant MeSH terms: Carcinoma; Neoplasms; Carcinoma, Basal Cell; Skin Neoplasms

Study Results

Participant Flow

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Period Title: Overall Study
STARTED	24
COMPLETED	17
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Overall Participants	24
Age, Customized (Count of Participants)
50-59 years old	5 20.8%
60-69 years old	8 33.3%
70-79 years old	4 16.7%
80-89 years old	6 25%
90-99 years old	1 4.2%
Sex: Female, Male (Count of Participants)
Female	6 25%
Male	18 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	15 62.5%
Unknown or Not Reported	9 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	14 58.3%
More than one race	0 0%
Unknown or Not Reported	9 37.5%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Local-regional Control Rate
Description	The local-regional control rate at 12 months from protocol therapy completion, defined as absence of progressive disease within the irradiated planning tumor volumes (PTV) for patients with locally advanced basal cell carcinoma in the head and neck.
Time Frame	Up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	17
Number [percentage]	100

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Estimate of the probability of PFS, with failure defined as any disease recurrence or death due to any cause with each duration measured from the time of first treatment with vismodegib to 12 months after completion of study treatment
Time Frame	From treatment start up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	17
Number [probability of progression-free survival]	1.00

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Estimate of the probability of OS, with failure defined as any disease recurrence or death due to any cause with each duration measured from the time of first treatment with vismodegib to 12 months after completion of study treatment
Time Frame	From treatment start up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	17
Number [probability of survival]	1.00

4. Secondary Outcome

Title	Percentage of Patients by Treatment-Related Adverse Events by Event Description
Description	The percentage of any adverse events (CTCAE, v. 4.0) assessed to be definitely, probably, or possibly related to vismodegib or its combination with radiation therapy at any point during protocol therapy or during the followup period.
Time Frame	up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	24
Grade 4 eye disorder	4
Grade 3 hyponatremia	13
Grade 3 oral mucositis	8
Grade 3 Gastrointestinal disorder	8
Grade 3 Dermatologic disorder	8
Grade 3 Abnormal Liver function	4
Grade 3 Anemia	4
Grade 3 Hypertension	4
Grade 2 Dermatitis	33
Grade 2 Dysgeusia	33
Grade 2 Myalgia	25
Grade 2 Fatigue	21
Grade 2 Oral mucositis	21
Grade 2 Weight Loss	17

5. Secondary Outcome

Title	Percentage of Patients by Adverse Event Not Related to Disease Progression
Description	The percentage of patients experiencing Grade 4-5 adverse events classified using CTCAE v.4.1 assessed to be definitely, probably, or possibly related to the induction or concurrent treatment components of the protocol regimen (that is not definitely related to disease progression) at any point during protocol therapy or during the followup period
Time Frame	up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

Only 1 patient experienced an adverse event (Grade 4 Eye Disorder) not related to disease progression

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	17
Number [percentage of participants]	6 25%

6. Secondary Outcome

Title	Number of Patients Discontinuing Treatment Due to Toxicity
Description	Feasibility of administering concurrent vismodegib with radiation therapy was assessed by the number of patients discontinuing treatment due to toxicity during the concurrent administration of vismodegib and radiation therapy (<75% of planned radiation therapy delivered)
Time Frame	up to 6 months from treatment start

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	24
Count of Participants [Participants]	5 20.8%

7. Secondary Outcome

Title	Clinical Response Rate
Description	Response rate (as per RECIST) of the primary site and regionally involved areas following all treatment components at 3 months after the completion of protocol therapy will be reported as a percentage of the total sample.
Time Frame	Up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	17
Number [percentage of patients]	88

8. Secondary Outcome

Title	Percentage of Patients With a Decrease of Basal Cell Carcinoma (BCC)
Description	Proportion of patients with a decrease of BCC within the irradiated planning tumor volumes (PTV) in patients who complete initial combined therapy, indicating a clinical response to vismodegib and radiation therapy
Time Frame	Up to 12 months after completing therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
Measure Participants	17
Number [percentage of patients]	88

Adverse Events

Time Frame	Up to 12 months
Arm/Group Title	Vismodegib and Radiation Therapy
Arm/Group Description	150mg Vismodegib will be taken once a day, daily. Radiation therapy will be started after the patient has completed taking vismodegib for 12 weeks. The patient will take daily vismodegib through the completion of radiation therapy. The patient will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes. After 12 weeks, they will be evaluated again to make sure they are still eligible to participate in the study. If they are eligible to continue, they will continue taking vismodeib daily as before for another 7 weeks while they receive radiation therapy.
All Cause Mortality
	Vismodegib and Radiation Therapy
	Affected / at Risk (%)	# Events
Total	1/24 (4.2%)
Serious Adverse Events
	Vismodegib and Radiation Therapy
	Affected / at Risk (%)	# Events
Total	4/24 (16.7%)
Eye disorders
Corneal ulcer	1/24 (4.2%)	1
Gastrointestinal disorders
Gastric hemorrhage	1/24 (4.2%)	1
Metabolism and nutrition disorders
Hyponatremia	2/24 (8.3%)	2
Vascular disorders
Abdominal Aortic Aneurysm	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Vismodegib and Radiation Therapy
	Affected / at Risk (%)	# Events
Total	24/24 (100%)
Cardiac disorders
Palpitations	2/24 (8.3%)	2
Eye disorders
Blurred vision	2/24 (8.3%)	2
Dry eye	2/24 (8.3%)	2
Eye disorders - Other	2/24 (8.3%)	3
Gastrointestinal disorders
Mucositis oral	8/24 (33.3%)	16
Dry mouth	5/24 (20.8%)	8
Nausea	5/24 (20.8%)	6
Constipation	4/24 (16.7%)	4
Diarrhea	2/24 (8.3%)	3
Dysphagia	2/24 (8.3%)	2
General disorders
Fatigue	19/24 (79.2%)	26
General disorders and administration site conditions - other	4/24 (16.7%)	12
Edema face	2/24 (8.3%)	2
Facial pain	2/24 (8.3%)	2
Injury, poisoning and procedural complications
Dermatitis radiation	11/24 (45.8%)	18
Investigations
Weight loss	10/24 (41.7%)	13
Alanine aminotransferase increased	2/24 (8.3%)	2
Creatinine increased	2/24 (8.3%)	3
Metabolism and nutrition disorders
Anorexia	7/24 (29.2%)	9
Hypokalemia	2/24 (8.3%)	2
Hyponatremia	3/24 (12.5%)	9
Musculoskeletal and connective tissue disorders
Myalgia	18/24 (75%)	22
Superficial soft tissue fibrosis	2/24 (8.3%)	2
Trismus	2/24 (8.3%)	2
Nervous system disorders
Dysgeusia	19/24 (79.2%)	30
Headache	4/24 (16.7%)	4
Peripheral sensory neuropathy	4/24 (16.7%)	5
Dizziness	2/24 (8.3%)	2
Memory impairment	2/24 (8.3%)	4
Psychiatric disorders
Depression	2/24 (8.3%)	2
Respiratory, thoracic and mediastinal disorders
Epistaxis	4/24 (16.7%)	5
Cough	3/24 (12.5%)	3
Nasal Congestion	2/24 (8.3%)	2
Skin and subcutaneous tissue disorders
Alopecia	9/24 (37.5%)	9
Pruritus	4/24 (16.7%)	5
Pain of skin	2/24 (8.3%)	2
Vascular disorders
Hypertension	4/24 (16.7%)	5
Hypotension	2/24 (8.3%)	2

Limitations/Caveats

[Not Specified]

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.