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

NCT01835626 | Completed Phase 2 Results DMC

• 2 other identifiers: 122011NCI-2013-00871
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Locally Advanced Basal Cell Carcinoma; Skin Cancer; Cutaneous Malignancy

Keywords

Locally advanced basal cell carcinoma; Skin cancer; Radiation therapy; Vismodegib; Head and neck cancer; Cutaneous malignancy

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Local-regional Control Rate

  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.

  Up to 12 months after completing therapy

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  From treatment start up to 12 months after completing therapy

• Overall Survival (OS)

  From treatment start up to 12 months after completing therapy

• Percentage of Patients by Treatment-Related Adverse Events by Event Description

  up to 12 months after completing therapy

• Percentage of Patients by Adverse Event Not Related to Disease Progression

  up to 12 months after completing therapy

• Number of Patients Discontinuing Treatment Due to Toxicity

  up to 6 months from treatment start

Study Arms (1)

Vismodegib and Radiation Therapy

EXPERIMENTAL

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; Radiation: Radiation therapy

Interventions

Vismodegib DRUG

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.

Also known as: Erivedge

Vismodegib and Radiation Therapy

Radiation therapy RADIATION

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.

Vismodegib and Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Zubrod Performance Status 0-2
• Age of greater than or equal to 18 years
• Adequate bone marrow and organ function defined as follows:
• Adequate bone marrow function:

You may not qualify if:

• 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.
• Patients with nevoid BCC syndrome (Gorlin syndrome) should not enroll in this study.
• 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.
• Prior vismodegib or other antagonists of the Hh pathway;
• 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.
• Recent (within 4 weeks of Registration), current, or planned participation in another experimental drug study.
• 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
• 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
• 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).

Sponsors & Collaborators

• Sue Yom: lead
• Genentech, Inc.: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Skin Neoplasms; Head and Neck Neoplasms

Interventions

HhAntag691; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Dr. Sue Yom
• Organization: University of California, San Francisco

Sue.Yom@ucsf.edu

(415) 353-9893

Study Officials

• Sue Yom, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Department of Radiation Oncology

Study Record Dates

• First Submitted: April 10, 2013
• First Posted: April 19, 2013
• Study Start: May 1, 2013
• Primary Completion: September 10, 2019
• Study Completion: September 10, 2019
• Last Updated: May 3, 2021
• Results First Posted: October 5, 2020

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)