MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02096471
• Date of registration: 12/03/2014
• Prospective Registration: Yes
• Primary sponsor: University of Alabama at Birmingham
• Public title: MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1 MEK Inhibitor
• Scientific title: A Phase 2 Trial of the MEK Inhibitor PD-0325901 in Adolescents and Adults With NF1-Associated Morbid Plexiform Neurofibromas
• Date of first enrolment: June 2014
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02096471
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- All studies to determine eligibility must be performed within 2 weeks prior to
enrollment unless otherwise indicated below. All clinical and laboratory data required
for eligibility of a subject must be available in the subject's medical or research
record.

- All subjects must have EITHER the clinical diagnosis of NF1 using the NIH Consensus
Conference criteria OR have a constitutional NF1 mutation documented in a CLIA/CAP
certified lab.

- Subjects must have plexiform neurofibroma(s) that are progressive OR are causing
significant morbidity, such as (but not limited to) head and neck lesions that are
compromising the airway or great vessels, brachial or lumbar plexus lesions that are
causing nerve compression and loss of function, lesions causing major deformity (e.g.,
orbital lesions) or are significantly disfiguring lesions of the extremity that cause
limb hypertrophy or loss of function, and painful lesions. Subjects with paraspinal
plexiform neurofibromas will be eligible for this trial. Histologic confirmation of
tumor is not necessary in the presence of consistent clinical and radiographic
findings

- For subjects enrolled for tumor progression, progression is defined as:

- Presence of new plexiform neurofibroma on MRI or CT (documented by comparison
with prior MRI or CT), OR

- A measurable increase in plexiform neurofibroma size (= 20% increase in the
volume, or a = 13% increase in the product of the two longest perpendicular
diameters, or a = 6% increase in the longest diameter) documented by comparison
of two scans (MRI or CT) approximately one year or less prior to evaluation for
this study.

- For subjects enrolled for a "major deformity" or "significantly disfiguring" tumor,
eligible tumors will be limited to tumors of the head & neck or those on other areas
of the body that are unable to be concealed by standard garments. In order to enroll a
plexiform neurofibroma for these indications, the Study Chair or Co-Chair must be
contacted to review subject eligibility prior to enrollment.

- Measurable disease: Subjects must have measurable plexiform neurofibroma(s) amenable
to volumetric MRI analysis. The target lesion must be seen on at least 3 consecutive
MRI slices and the field of view must contain the entire tumor of interest. Tumors
must be at least 3 mL in volume (most PNs 3 cm in longest diameter will meet this
criteria). If the tumor is <3 cm in longest diameter, the subject may still be
eligible. Central review of the MRI of the target plexiform is required prior to
enrollment to ensure that the tumor is measurable and amenable to volumetric analysis.
After consenting, images will be sent for Central review

- Age: Subjects must be = 16 years of age at the time of study entry.

- Durable Power of Attorney: Adults who are unable to provide informed consent will NOT
be enrolled on this study.

- Performance Level: Karnofsky greater than or equal to 50% Note: Subjects who are
unable to walk because of paralysis, but who are up in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score.

- Prior Therapy: Subjects are only eligible if complete resection of a plexiform
neurofibroma with acceptable morbidity is not feasible, or if a subject with surgical
option refuses surgery.

- Subjects who underwent surgery for a progressive plexiform neurofibroma will be
eligible to enter the study after the surgery, provided the plexiform neurofibroma was
incompletely resected and is evaluable by volumetric analysis.

- Subjects may have been previously treated for a plexiform neurofibroma or other
tumor/malignancy, but must have fully recovered from the acute toxic effects of all
prior chemotherapy or radiotherapy prior to entering this study.

- Myelosuppressive chemotherapy: Must not have received within 4 weeks of entry onto
this study.

- Hematopoietic growth factors: At least 7 days since the completion of therapy with a
growth factor that supports platelet, red or white cell number or function.

- Biologic (anti-neoplastic agent): At least 14 days since the completion of therapy
with a biologic agent. These subjects must be discussed with the Study Chair on a
case-by-case basis.

- Investigational Drugs: Subjects must not have received an investigational drug within
4 weeks.

- Steroids: Subjects with endocrine deficiencies are allowed to receive physiologic or
stress doses of steroids if necessary.

- 6 months from involved field radiation to index plexiform neurofibroma(s); 6 weeks
must have elapsed if subject has received radiation to areas outside index plexiform
neurofibroma(s). Subjects who have received radiation to the orbit at any time are
excluded.

- Surgery: At least 2 weeks since undergoing any major surgery and must be recovered
from effects of surgery.

- Organ Function Requirements

- Adequate Bone Marrow Function

- Adequate Renal Function

- Adequate Liver Function

Exclusion Criteria:

- Chronic treatment with systemic steroids or another immunosuppressive agent. Subjects
with endocrine deficiencies are allowed to receive physiologic or stress doses of
steroids if necessary.

- Evidence of an active optic glioma or other low-grade glioma, requiring treatment with
chemotherapy or radiation therapy. Subjects not requiring treatment are eligible for
this protocol.

- Patients with malignant glioma, malignant peripheral nerve sheath tumor, or other
malignancy requiring treatment in the last 12 months.

- Subjects who have received radiation to the orbit at any time previously

- Subjects with glaucoma, intraocular pressure >21 mmHg, or any other significant
abnormality on ophthalmic examination (performed by an ophthalmologist).

- Ophthalmological findings secondary to long-standing Optic Pathway Glioma such as
optic nerve pallor or strabismus will NOT be considered significant for the purposes
of the study.

- Tumor not able to be reliably evaluated by volumetric analysis.

- Other concurrent severe and/or uncontrolled medical disease, which could compromise
participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension,
severe infection, severe malnutrition, chronic liver or renal disease, active upper GI
tract ulceration, congestive heart failure, etc.)




Age minimum: 16 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neurofibromatosis Type 1 and Growing or Symptomatic, Inoperable PN

Intervention(s)

Drug: PD-0325901

Primary Outcome(s)

Percent of Participants With a 20% or More Change in Target Tumor Volume [Time Frame: baseline to 24 months]

Secondary Outcome(s)

Area Under the Curve for the Parent Compound [Time Frame: Day 1; Course 1]

Evaluable Participants Treated With PD-0325901 [Time Frame: baseline to 24 months]

Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments [Time Frame: Baseline to 12 Months]

Mean Half-Life for the PD-0325901 Concentrations [Time Frame: Day 1; Course 1]

Toxicity of PD-0325901 [Time Frame: Baseline to 24 Months]

Area Under the Curve for the Metabolite Compound [Time Frame: Day 1; Course 1]

The Objective Response Rate of up to 2 Non-Target Plexiform Neurofibromas to PD-0325901 [Time Frame: Baseline to 24 Months]

Secondary ID(s)

WI176190

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/01/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02096471