Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01774253
• Collaborator: Phoenix Children's Hospital (Other)
• Enrollment: 9
• Locations: 2
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate an investigational drug (Vismodegib) for Pontine Glioma that is growing or has come back (reoccurred). This study will look at the tumors response to the study drug, Vismodegib, and will also look at the safety and tolerability of Vismodegib.

Vismodegib has been tested in multiple adult clinical trials and one pediatric trial. Laboratory testing in pontine gliomas suggests that this drug may be effective in treating this disease.

Condition or Disease	Intervention/Treatment	Phase
Pontine Glioma	Drug: Vismodegib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open-label, Multi-center Study of Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma.
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vismodegib Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated.	Drug: Vismodegib; Other Names: Erivedge

Outcome Measures

Primary Outcome Measures

1. Number of Days Participants Experienced Progression Free Survival (PFS) [5 years]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.

Secondary Outcome Measures

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [2 years]

   To determine the safety and tolerability of Vismodegib as a single agent in pediatric and young adult patients with refractory or recurrent pontine glioma

2. Determine the Median Overall Survival (OS) of Participants [2 years]

   Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)

3. Evaluate the Impact of Quality of Life of Children Receiving Vismodegib Using PedsQL Questionnaires [2 years]

   Evaluate the impact of Quality of Life of children receiving Vismodegib using PedsQL questionnaires

4. Determine the Response Rates of Participants Based on Activation (or no Activation) of Their Hedgehog Signaling Pathway [3 years]

   To determine the objective response rates (partial and complete response) for patients without and with evidence of activation of Hedgehog signaling pathway in their tumors

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have radiographically proven diffuse intrinsic pontine glioma and confirmation of residual disease after initial therapy or at the time of recurrence/progression as confirmed by MRI of the brain

• Subjects must be age ≥3 years and ≤ 18 years

• Diffuse intrinsic pontine glioma with measurable disease after receiving radiotherapy either concurrent with or followed by ≤ 2 prior courses of chemotherapy

• Measurable disease as defined by:

Measurable tumor >10mm by MRI

• Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)

• Body surface area > 0.67 m2 and ≤ 2.21 m2

• Life expectancy of at least 2 months

• A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)

• Acceptable liver function as defined by:

1. Bilirubin ≤ 1.5 times upper limit of normal

2. AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age as follows:

• 0.8 mg/dL (for patients ≤ 5 years of age)

• 1.0 mg/dL (for patients 6 to 10 years of age)

• 1.2 mg/dL (for patients 11 to 15 years of age)

• 1.5 mg/dL (for patients > 15 years of age)

• Acceptable hematologic status as defined by:

1. Granulocyte ≥ 1500 cells/mm3

2. Platelet count ≥ 100,000 (plt/mm3)

3. Serum albumin ≥ 2.5 g/dL

• Urinalysis:

1. No clinically significant abnormalities

• Acceptable coagulation status as defined by:

1. PT/INR less than 1.5

2. PTT within normal limits

• Subjects must be able to swallow and retain oral medication

• Female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for 7 (seven) months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots).

• Male post-pubertal study subjects need to agree to use condoms with spermicide, even after a vasectomy, during sexual intercourse with female partners while being treated with Erivedge capsule and for 2 months after the last dose to avoid exposing an embryo or fetus to Vismodegib.

• Voluntarily signed and dated a written IRB-approved informed consent by parent or legal guardian of subject

Exclusion Criteria:

• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for generally about 3 weeks (8 weeks for radiotherapy) prior to the first dose of study medication, as well as recovered from toxicity (to ≤ than grade 2 except for alopecia) induced by previous treatments.

• Currently receiving another investigational medicinal product.

• Uncontrolled concurrent illness including, but not limited to:

1. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy

2. Diarrhea of any cause ≥ CTCAE grade 2

3. Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary

4. Any kind of malabsorption syndrome significantly affecting gastrointestinal function

• Pregnant or nursing female patients. NOTE: If a female patient becomes pregnant or suspects that she is pregnant while participating in this study, she should stop taking study drug and immediately inform her treating physician immediately.

• Prior therapy with a Hedgehog inhibitor

• Unwillingness or inability to comply with procedures required in this protocol

• Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.

• History of Congestive Heart Failure (CHF) or ventricular arrhythmia requiring medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503

Sponsors and Collaborators

• Wake Forest University Health Sciences
• Phoenix Children's Hospital

Investigators

• Study Chair: Giselle Sholler, MD, Beat Childhood Cancer at Atrium Health
• Principal Investigator: Albert Cornelius, MD, Helen DeVos Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Beat Childhood Cancer

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01774253
• Other Study ID Numbers: NMTRCPG007
• First Posted: Jan 23, 2013
• Last Update Posted: Apr 22, 2022
• Last Verified: Nov 1, 2020

• Keywords provided by Wake Forest University Health Sciences: DIPG
• Additional relevant MeSH terms: Glioma

Study Results

Participant Flow

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Period Title: Overall Study
STARTED	9
COMPLETED	0
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Overall Participants	9
Age (Count of Participants)
<=18 years	9 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 11.1%
Not Hispanic or Latino	7 77.8%
Unknown or Not Reported	1 11.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 88.9%
More than one race	0 0%
Unknown or Not Reported	1 11.1%

Outcome Measures

1. Primary Outcome

Title	Number of Days Participants Experienced Progression Free Survival (PFS)
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Measure Participants	4
Median (Full Range) [Days]	60

2. Secondary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description	To determine the safety and tolerability of Vismodegib as a single agent in pediatric and young adult patients with refractory or recurrent pontine glioma
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Measure Participants	9
Number [participants]	4 44.4%

3. Secondary Outcome

Title	Determine the Median Overall Survival (OS) of Participants
Description	Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Not evaluated due to early closure. Study data does not exist.

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Measure Participants	0

4. Secondary Outcome

Title	Evaluate the Impact of Quality of Life of Children Receiving Vismodegib Using PedsQL Questionnaires
Description	Evaluate the impact of Quality of Life of children receiving Vismodegib using PedsQL questionnaires
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

QOL's not collected due to early closure of study. Data not collected or analyzed threfore no data exists.

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Measure Participants	0

5. Secondary Outcome

Title	Determine the Response Rates of Participants Based on Activation (or no Activation) of Their Hedgehog Signaling Pathway
Description	To determine the objective response rates (partial and complete response) for patients without and with evidence of activation of Hedgehog signaling pathway in their tumors
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

No samples collected for hedgehog pathway. No data exists.

Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
Measure Participants	0

Adverse Events

Time Frame	New adverse events collected from first dose of study drug to 30 days past last dose of study drug. Related adverse events followed until resolution.
Arm/Group Title	Vismodegib
Arm/Group Description	Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated. Vismodegib
All Cause Mortality
	Vismodegib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vismodegib
	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)
General disorders
Choking event resulting in death	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Vismodegib
	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)
Blood and lymphatic system disorders
Increased GGT	1/9 (11.1%)	1
Gastrointestinal disorders
Diarrhea	1/9 (11.1%)	1
Gastoesophageal Reflux Disease	1/9 (11.1%)	1
Vomiting	1/9 (11.1%)	1
General disorders
Alopecia	1/9 (11.1%)	1
Fatigue	1/9 (11.1%)	1
Nervous system disorders
Ataxia	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Rash	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.