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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of California, San Francisco
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Sue Yom, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01835626
First received: April 10, 2013
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Locally Advanced Basal Cell Carcinoma
Skin Cancer
Cutaneous Malignancy
Drug: Vismodegib
Radiation: Radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Local-regional control from therapy completion [ Time Frame: About 18 months ] [ Designated as safety issue: No ]
    To determine local-regional control rate at 12 months from protocol therapy completion, defined as complete or partial response, with 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:
  • Probability of progression-free survival [ Time Frame: About 18 months ] [ Designated as safety issue: No ]
    Failure is defined as any disease recurrence or death due to any cause, and OS with the duration for each measured from the time of first treatment with vismodegib to 12 months after completion of study treatment.

  • Initial toxicity during the 3 months immediately after completion of protocol therapy. [ Time Frame: About 3 months ] [ Designated as safety issue: Yes ]
  • Feasibility of administering concurrent vismodegib with radiation therapy determined by the proportion of patients discontinuing treatment due to toxicity during the study [ Time Frame: About 6 months ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: About 3 months ] [ Designated as safety issue: No ]
  • Clinical response to vismodegib and radiation therapy determined by the proportion of patients with a decrease of basal cell carcinoma within the irradiated planning tumor volumes in patients who completed therapy [ Time Frame: About 18 months ] [ Designated as safety issue: No ]
  • Adverse events reported during the drug-alone and combined-modality components of the protocol regimen during treatment [ Time Frame: about 18 months ] [ Designated as safety issue: Yes ]
    This will be assessed by the number and attribution of all adverse events, (including vital signs, physical findings, and clinical laboratory results, CTCAE, v 4.1) in patients who receive any amount of study drug and radiation therapy.

  • Proportion of any adverse events (CTCAE, v. 4.1) assessed to be related during the drug-alone and combined-modality components of the protocol regimen during treatment [ Time Frame: About 18 months ] [ Designated as safety issue: Yes ]
  • Proportion of patients experiencing Grade 4-5 adverse events related to the induction or concurrent treatment components of the protocol regimen (that is not definitely related to disease progression) [ Time Frame: About 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: May 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vismodegib and Radiation Therapy
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 Name: 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.

Detailed Description:

This is a single arm, multi-centered 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 BCC

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

    Adequate bone marrow function:

    leukocytes: > 3,000/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 ULN or within 3x the ULN for patients with Gilbert disease AST(SGOT): < 3 X institutional upper limit of normal ALT(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

  6. 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.

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. Known other malignancy within 3 years (except for tumors with a negligible risk for metastasis or death, such as adequately treated basal cell or squamous cell carcinoma of the skin, ductal carcinoma in situ of the breast, carcinoma in situ of the cervix, differentiated thyroid carcinoma considered in remission, or the presence of prostate cancer confined to the prostate with a PSA < 1 for more than 6 months; the presence of other stage I basal cell carcinomas is allowed);
  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.
  6. Recent (within 4 weeks of Registration), current, or planned participation in another experimental drug study.
  7. 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
  8. 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
  9. 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.
  10. Life expectancy of <12 weeks
  11. 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.

  12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements;
  13. 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
  14. HIV-positive patients on combination antiretroviral therapy, because of the potential for pharmacokinetic interactions with vismodegib;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01835626

Contacts
Contact: Romobia Hutchinson 415-353-4294 HutchinsonR@cc.ucsf.edu
Contact: Frances Zhang 415-353-9857 FZhang@radonc.ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Romobia Hutchinson    415-353-4294    HutchinsonR@cc.ucsf.edu   
Contact: Frances Zhang    415-353-9857    FZhang@radonc.ucsf.edu   
Principal Investigator: Sue Yom, MD         
Sub-Investigator: Sarah Arron, MD, PhD         
Sub-Investigator: Alain Algazi, MD         
Sponsors and Collaborators
Sue Yom
Genentech
Investigators
Principal Investigator: Sue Yom, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Sue Yom, Associate Professor, Department of Radiation Oncology, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01835626     History of Changes
Other Study ID Numbers: CC#122011
Study First Received: April 10, 2013
Last Updated: April 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by 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:
Neoplasms
Carcinoma
Skin Neoplasms
Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Skin Diseases
Neoplasms, Basal Cell

ClinicalTrials.gov processed this record on August 18, 2014