Vismodegib in Treating Patients With Steroid-Refractory Chronic Graft-Versus-Host Disease

NCT02337517 | Terminated Phase 2 Results

• 5 other identifiers: NCI-2014-02672IIT 9664845849664P30CA042014
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This pilot clinical trial studies how well vismodegib works in treating patients with chronic graft-versus-host disease that did not respond to previous steroid treatment. Chronic graft-versus-host disease can cause a build-up of scar tissue under the skin and lead to symptoms such as sclerodermatous skin changes, dry mouth, dry eye, narrowing of the esophagus, or vaginal graft-versus-host disease. Vismodegib may work against the build-up of scar tissue and be a better treatment for chronic graft-versus-host disease caused by a hematopoietic stem cell transplant.

Conditions

Chronic Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Failure Free Survival (FFS)

  Defined as the count of participants at six months with an absence of non relapse mortality (NRM), no recurrent malignancy, steroid dose at 6 months =\< 0.2 mg/kg/day of prednisone dose equivalent (PDE), and no addition of new systemic treatment for chronic graft-versus-host disease (GVHD) at six months after start of treatment.

  At 6 months

Secondary Outcomes (7)

• Incidence of Adverse Events

  Up to 1 month post last date of treatment (max time of approximately one year)

• Chronic Graft-versus-host Disease Response

  Baseline to up to 12 months after initiation of protocol therapy

• One-year Non Relapse Mortality (NRM)

  At 1 year

• One Year Relapse

  Up to one year

• One-year Failure Free Survival (FFS)

  At 1 year

Study Arms (1)

Supportive care (vismodegib)

EXPERIMENTAL

Patients receive vismodegib PO daily, every other day, every three days, or twice weekly for 6-12 months in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Vismodegib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Supportive care (vismodegib)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

Supportive care (vismodegib)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 months
• Leukocytes \>= 3,000/microliter (mcL)
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 50,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2.5 x institutional upper limit of normal
• Creatinine =\< 1.5 mg/dl OR creatinine clearance \>= 55 mL/min using the Cockcroft-Gault equation for patients with creatinine levels above 1.5 mg/dl
• Patients with chronic GVHD diagnosed within 3 years after hematopoietic stem cell transplant (HSCT) for any disease, with any graft, and any conditioning regimen with at least one manifestation secondary to fibrosis, including: sclerodermatous skin changes, dry mouth, dry eye, esophageal strictures, or vaginal GVHD
• Failure to respond to corticosteroids, defined as:
• Progression of chronic GVHD despite optimal first line therapy (\> 0.5 mg/kg/day of prednisone dose equivalent (PDE) for two weeks) or
• No improvement after 4-8 weeks of sustained therapy; sustained therapy should include 2 weeks of \> 0.5 mg/kg/day of PDE or
• Inability to taper steroid dosage to less than 0.5 mg/kg/day of PDE without worsening of chronic GVHD or
• Need for second or third line therapy beyond corticosteroids and calcineurin inhibitors or sirolimus, irrespective of other criteria
• Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 24 months post-treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who are receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449
• Patients receiving any medications or substances that are strong inducers/inhibitors or substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/5, cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), CYP2C8, or CYP2C19 are ineligible; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
• Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis are ineligible
• Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GDC-0449
• More than 2 lines of therapy beyond corticosteroids with or without calcineurin inhibitors or sirolimus
• Relapsed malignancy after transplantation

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Genentech, Inc.: collaborator

Study Sites (2)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: Data Manager
• Organization: HCI Research Compliance Office

compliance@hci.utah.edu

8015850601

Study Officials

• Daniel R Couriel

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2015
• First Posted: January 13, 2015
• Study Start: September 8, 2015
• Primary Completion: June 28, 2018
• Study Completion: June 28, 2018
• Last Updated: July 19, 2021
• Results First Posted: June 16, 2021

Record last verified: 2021-06

Locations

US (2)