search
Back to results

Cyclin-Dependent Kinase (CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type I (NF1) Related Atypical Neurofibromas

Primary Purpose

Neurofibromatosis 1

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Abemaciclib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neurofibromatosis 1 focused on measuring Kinase Inhibitor, distinct nodular lesion, genomic alteration

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • INCLUSION CRITERIA:
  • Patients must have a clinical diagnosis of NF1, i.e., patients must have at least two of the diagnostic criteria for NF1 listed below (NIH Consensus conference) or a confirmed

NF1 mutation from a CLIA-certified laboratory:

-- Six or more cafe-au-lait macules (>= 0.5cm in prepubertal subjects or >= 1.5 cm

in post pubertal subjects)

  • Freckling in axilla or groin
  • A neurofibroma or plexiform neurofibroma
  • Optic glioma
  • Two or more Lisch nodules
  • A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
  • A first-degree relative with NF1

    • Presence of >= 1 ANF (biopsy confirmed) for whom surgical removal could cause significant clinical morbidity OR for which patient is unwilling to undergo surgical resection OR the presence of more than one distinct nodular lesion (DNL) including at least 1 biopsy proven ANF

NOTES: Definition of DNL. In addition, there will not be a requirement for confirmed CDKN2A/B deletion for study eligibility due to known biopsy sampling error and tumor heterogeneity.

  • Age >= 12 years old (no maximum age) with associated age-related requirements as follows:
  • Age >= 12 years old with BSA >= 0.71 M^2 and able to swallow whole tablets
  • Willingness of patients >= 12 years old and <18 years old to undergo pre-treatment percutaneous biopsy of ANF if deemed feasible with minimal morbidity
  • Willingness of patients >=18 years old to undergo pre-treatment and on-treatment percutaneous biopsy of ANF if deemed feasible with minimal morbidity

NOTE: For patients of all ages with ANF that cannot be safely biopsied with minimal morbidity, biopsy requirement to be performed at NIH Clinical Center will be waived from eligibility criteria. In this case, review of available archival tissue by NIH Pathology will be necessary to confirm diagnosis of ANF, which is mandatory for eligibility.

  • Measurable disease: Patients must have at least one measurable ANF defined as a lesion of at least 3 centimeters (cm) measured in one dimension. Measurability and suitability for volumetric MRI analysis of the target ANF must be confirmed with the NCI POB prior to enrolling a patient. The target ANF will be defined as the clinically most relevant ANF, which has to be amenable to volumetric MRI analysis.

    - Prior Therapies:

  • Since there is no standard effective chemotherapy for patients with NF1 and ANF, patients may be treated on this trial without having received prior medical therapy directed at their ANF.
  • Investigational agents/biologic therapies (not chemotherapy): Patients who have received previous investigational agents or biologic therapies are eligible for enrollment. At least 30 days or 5 half-lives must have elapsed since receiving medical therapy directed at any NF1 related tumor. Patients who received prior medical therapy for a NF1 related tumor manifestation must have recovered from the acute toxic effects of all prior therapy to grade 1 CTCAEv5 except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment before entering this study.
  • Chemotherapy agents: Patients who received chemotherapy must have recovered (CTCAE Grade <=1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 28 days is required between last chemotherapy dose and enrollment (provided the patient did not receive radiotherapy).
  • Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. Patients who have received previous radiation therapy are eligible for enrollment. At least 6 weeks must have elapsed since the last radiation therapy and start of treatment. The only target ANF cannot have received radiation previously.
  • At least 28 days must have elapsed since any major surgeries, with evidence of good wound healing. Minimally invasive biopsies and central line placements are not considered major surgeries.
  • Patients who have received prior treatment with abemaciclib or another specific CDK4/6 inhibitor are not eligible for enrollment

    • Adequate performance scale (Lansky/Karnofsky >=70%).
    • Adequate organ function as defined below:
  • Hematologic Function: Patients must have an absolute neutrophil count >= 1500/mililiters, hemoglobin >= 9 g/dL (transfusion independent, defined as not receiving blood transfusion unless related to trauma or surgeries), and platelets less than or equal to 100,000/mililiters (transfusion independent, defined as not receiving platelet transfusions unless related to trauma or surgeries)
  • Hepatic Function: Patients must have bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST/ALT within <= 3 x upper limit of normal.
  • Renal Function: Patients must have a creatinine clearance or radioisotope GFR >=60ml/min/1.73 m^2 or a normal serum creatinine based on age, described below.
  • Age (years) is >12 and <=15 then Maximum Serum Creatinine (mg/dL) = 1.2
  • Age (years) is >15 then Maximum Serum Creatinine (mg/dL) = 1.5
  • Cardiac Function: Normal ejection fraction (ECHO or cardiac MRI) >= 53% (or the institutional normal; if a range is given then the upper value of the range will be used); QTC or QTcF <=450 msec.

    • Willingness to avoid grapefruit or grapefruit juice during abemaciclib administration
    • Informed Consent: Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. All patients or their legal guardians (if the patient is < 18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions.
    • Based on animal studies, the effects of abemaciclib can cause fetal harm. For these reasons, women of child-bearing potential and men must agree to use a highly effective contraceptive method during treatment and for at least 3 months after the last dose of abemaciclib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of abemaciclib administration
  • Woman subjects of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib.
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Contraceptive methods may include intrauterine devices (IUD), or barrier method, a spermicidal agent should be added as a double barrier protection; abstinence is also acceptable.
  • Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation she must discontinue treatment immediately. Data on fetal outcomes and breastfeeding are to be collected for regulatory reporting and drug safety evaluation.

EXCLUSION CRITERIA:

  • Pregnant women, or women who intend to become pregnant during the study, are excluded from this study because of the teratogenic effects of abemaciclib. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study.
  • May not have a NF1-related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy or surgery.
  • Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel that would preclude adequate absorption, or preexisting Crohn s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses or renal transplant, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
  • Active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Patients with HIV who have adequate CD4 counts and who have no requirement for antiviral therapy will be eligible. NOTE: Screening is not required for enrollment.
  • Patients with interstitial lung disease
  • Requires treatment with strong CYP3A inhibitors or inducers
  • Inability to swallow tablets, since tablets cannot be crushed or broken.
  • Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol (see Study Procedure Manual). Prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target ANF on MRI.
  • Refractory nausea and vomiting that would limit drug administration in the opinion of the Principal Investigator
  • Known severe hypersensitivity to abemaciclib or any excipient of abemaciclib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib
  • Clinical judgment by the investigator that the patient should not participate in the study

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1/ Phase I Dose Escalation

2/ Phase II Objective Response Rate

Arm Description

Abemaciclib orally twice daily at escalating doses to determine the MTD/RP2D

Abemaciclib orally twice daily at the RP2D

Outcomes

Primary Outcome Measures

safety of abemaciclib in patients with NF1 and a measurable ANF
List of adverse event frequency

Secondary Outcome Measures

Tolerability of abemaciclib on a prolonged dosing schedule
Duration of treatment and adverse event types and frequency
Stable disease rate of target ANF
Proportion of patients that have progressive disease
Response rate of non-target ANF/DNL
Changes in non-target ANF/DNL determined by volumetric MRI analysis
Effect of abemaciclib on CDK4/6 target inhibition
Measurement of phosphorylated Retinoblastoma (pRB) in tumor biopsy samples
Effect of abemaciclib on ANF related pain and quality of life
Patient-Reported Outcome response
Abemaciclib pharmacokinetics and pharmacodynamic
Drug level in blood

Full Information

First Posted
February 10, 2021
Last Updated
October 13, 2023
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04750928
Brief Title
Cyclin-Dependent Kinase (CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type I (NF1) Related Atypical Neurofibromas
Official Title
A Phase I/II Study of the Cyclin-Dependent Kinase(CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type 1 (NF1) Related Atypical Neurofibromas
Study Type
Interventional

2. Study Status

Record Verification Date
October 11, 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 29, 2021 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Background: NF1 is a genetic disease that causes tumors called atypical neurofibromas. These tumors, which arise from nerves, can cause serious medical problems. The only treatment is surgery. Researchers want to see if a drug called abemaciclib can help. Objective: To find a safe, tolerable dose of abemaciclib for treating atypical neurofibromas. Eligibility: People ages 12 and older who have NF1 and have one or more atypical neurofibromas that cannot or will not be removed with surgery Design: Participants will be screened with: Medical history and physical exam Blood, urine, and heart tests MRI: Participants will lie in a machine that takes pictures of the body. A padding or coil will be placed around their head. They may have a contrast agent injected into a vein. Biopsy sample: A small piece of tumor will be removed using a large needle. Participants will have frequent visits during the study. These will include repeats of the screening tests as well as the following: PET scan: Participants will lie in a machine that takes pictures of the body. They will have a contrast agent injected into their arm. Questionnaires about the effects of abemaciclib on pain and quality of life Possible photographs of tumors Participants will take abemaciclib capsules orally twice daily in 28-day cycles. They will take the drug for up to 2 years. Some may be able to take it for longer. Participants will have a follow-up visit about 30 days after their last dose of the study drug. Then they will have visits every 3 months for 1 year.
Detailed Description
Background: Neurofibromatosis type 1 (NF1) is a genetic tumor predisposition syndrome (incidence of 1:3000), which results in the development of progressive tumor and non-tumor manifestations, the majority of which have no effective medical therapies. 25-50% of individuals with neurofibromatosis type 1 (NF1) develop histologically benign plexiform neurofibromas (PN), which can cause substantial morbidity. Recently, the POB identified that MEK inhibitors cause shrinkage of the majority of PN and that PN shrinkage is associated with clinical benefit. A natural history study of NF1 at the NCI has gathered comprehensive imaging information using longitudinal whole-body MRI with volumetric measurements. By this approach, distinct nodular lesions (DNL) were identified, many of which are atypical neurofibromas (ANF) based on pathology review. The NCI POB and others have described ANF as precursor lesions for aggressive soft tissue sarcomas called malignant peripheral nerve sheath tumors (MPNST), which show poor response to chemotherapy and have poor survival. Of note, ANF appear to be less responsive to treatment with MEK inhibitors indicating a different biology. Exome sequencing of 16 ANF resected at the National Cancer Institute, Pediatric Oncology Branch (NCI POB) and Belgium revealed that 90% of the cases had heterozygous loss of CDKN2A/B as the only new somatic change in addition to biallelic NF1 deletion, consistent with prior reports. These results demonstrate that transformation of NF1 nerve tumors may genetically proceed through the premalignant ANF by a common mechanism that might be a point of intervention. CDKN2A is the primary inhibitory brake on CDK4/6 driven signaling and is commonly deleted in glioblastoma, pancreas, bladder, breast and prostate cancer. The specific CDK4/6 inhibitor, abemaciclib, has FDA approval for the treatment of metastatic breast cancer. ANF is a prototypic premalignant lesion for testing experimental intervention, as these lesions are at risk for transformation, and share a common potentially druggable genomic alteration (CDKN2A/B deletion). We propose a clinical trial of abemaciclib in children and adults with NF1 and unresectable ANF. Objectives: Phase I: To determine the recommended Phase II dose (RP2D) of abemaciclib in patients with NF1 and a measurable ANF. Phase II: To determine the objective response rate (ORR) in the target ANF; complete and partial response (CR + PR), response determined by volumetric MRI analysis (^3 20% volume reduction) compared to baseline. Eligibility: Patients must be at least 12 years of age with a diagnosis of NF1 with associated age-related requirements as follows: Willingness of patients >= 12 years old and <18 years old to undergo pre-treatment percutaneous biopsy of ANF if deemed feasible with minimal morbidity Willingness of patients >=18 years old to undergo pre-treatment and on-treatment percutaneous biopsy of ANF if deemed feasible with minimal morbidity Presence of >= 1 measurable ANF (biopsy confirmed) for which surgical removal could cause significant morbidity OR for which patient is unwilling to undergo surgical resection OR the presence of more than one distinct nodular lesion (DNL) including at least 1 biopsy proven ANF For patients of all ages with ANF who cannot be safely biopsied with minimal morbidity, biopsy requirement to be performed at NIH Clinical Center will be waived from eligibility criteria. In this case, review of available archival tissue by NIH Pathology will be necessary to confirm diagnosis of ANF, which is mandatory for eligibility. Design: This is a Phase I/II non-randomized, open label, single institution study of the CDK4/6 inhibitor, abemaciclib, in children and adults with NF1 and a measurable ANF or with multiple ANF/DNL. Primarily because the tolerability of investigational agents may differ between the NF1 population and non-NF1 population and secondarily because abemaciclib has not been evaluated in children to date, there will be a limited dose finding phase. During the Phase 1 portion of the trial, the first 6 subjects enrolled will be treated at 75% of the adult recommended Phase II dose (ARP2D; 150mg PO BID) of abemaciclib used in patients with malignancies, in a 28-day cycle. For patients < 18 years of age, dosing will be based on body surface area (BSA). Cohorts of up to 6 subjects will be enrolled, with dose adjustment depending on dose-limiting toxicities (DLT) until the maximum tolerated dose (MTD)/ recommended Phase II dose (RP2D) is established. The Phase II trial is a Simon minimax two-stage trial design. An observed response rate of approximately 30% or greater would be considered desirable. The first stage of the Phase II portion of the trial will enroll 15 evaluable subjects; if 0 to 2 of the 15 have a PR or CR, then no further subjects will be accrued. If 3 or more of the 15 subjects have a PR or CR, then accrual would continue until a total of 21 evaluable subjects have been enrolled in phase II. The accrual ceiling will be set at 50 eligible subjects (to include patients who are screened but found to not be eligible to undergo treatment). All patients will undergo careful toxicity monitoring. Restaging MRI for response will be performed pre-cycles 3 and 5, and then every 4 cycles for remainder of the first year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurofibromatosis 1
Keywords
Kinase Inhibitor, distinct nodular lesion, genomic alteration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1/ Phase I Dose Escalation
Arm Type
Experimental
Arm Description
Abemaciclib orally twice daily at escalating doses to determine the MTD/RP2D
Arm Title
2/ Phase II Objective Response Rate
Arm Type
Experimental
Arm Description
Abemaciclib orally twice daily at the RP2D
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Intervention Description
Abemaciclib is to be administered orally on Days 1 through 28 of each 28-day cycle
Primary Outcome Measure Information:
Title
safety of abemaciclib in patients with NF1 and a measurable ANF
Description
List of adverse event frequency
Time Frame
30 days after treatment
Secondary Outcome Measure Information:
Title
Tolerability of abemaciclib on a prolonged dosing schedule
Description
Duration of treatment and adverse event types and frequency
Time Frame
up to 2 years of treatment or until disease progression or unacceptable treatment-related toxicity
Title
Stable disease rate of target ANF
Description
Proportion of patients that have progressive disease
Time Frame
baseline through 30 days after treatment
Title
Response rate of non-target ANF/DNL
Description
Changes in non-target ANF/DNL determined by volumetric MRI analysis
Time Frame
at progression
Title
Effect of abemaciclib on CDK4/6 target inhibition
Description
Measurement of phosphorylated Retinoblastoma (pRB) in tumor biopsy samples
Time Frame
after Day 7 of Cycle 1
Title
Effect of abemaciclib on ANF related pain and quality of life
Description
Patient-Reported Outcome response
Time Frame
baseline through 30 days after treatment
Title
Abemaciclib pharmacokinetics and pharmacodynamic
Description
Drug level in blood
Time Frame
30 days after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Patients must have a clinical diagnosis of NF1, i.e., patients must have at least two of the diagnostic criteria for NF1 listed below (NIH Consensus conference) or a confirmed NF1 mutation from a CLIA-certified laboratory: -- Six or more cafe-au-lait macules (>= 0.5cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects) Freckling in axilla or groin A neurofibroma or plexiform neurofibroma Optic glioma Two or more Lisch nodules A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex) A first-degree relative with NF1 Presence of >= 1 ANF (biopsy confirmed) for whom surgical removal could cause significant clinical morbidity OR for which patient is unwilling to undergo surgical resection OR the presence of more than one distinct nodular lesion (DNL) including at least 1 biopsy proven ANF NOTES: Definition of DNL. In addition, there will not be a requirement for confirmed CDKN2A/B deletion for study eligibility due to known biopsy sampling error and tumor heterogeneity. Age >= 12 years old (no maximum age) with associated age-related requirements as follows: Age >= 12 years old with BSA >= 0.71 M^2 and able to swallow whole tablets Willingness of patients >= 12 years old and <18 years old to undergo pre-treatment percutaneous biopsy of ANF if deemed feasible with minimal morbidity Willingness of patients >=18 years old to undergo pre-treatment and on-treatment percutaneous biopsy of ANF if deemed feasible with minimal morbidity NOTE: For patients of all ages with ANF that cannot be safely biopsied with minimal morbidity, biopsy requirement to be performed at NIH Clinical Center will be waived from eligibility criteria. In this case, review of available archival tissue by NIH Pathology will be necessary to confirm diagnosis of ANF, which is mandatory for eligibility. Measurable disease: Patients must have at least one measurable ANF defined as a lesion of at least 3 centimeters (cm) measured in one dimension. Measurability and suitability for volumetric MRI analysis of the target ANF must be confirmed with the NCI POB prior to enrolling a patient. The target ANF will be defined as the clinically most relevant ANF, which has to be amenable to volumetric MRI analysis. - Prior Therapies: Since there is no standard effective chemotherapy for patients with NF1 and ANF, patients may be treated on this trial without having received prior medical therapy directed at their ANF. Investigational agents/biologic therapies (not chemotherapy): Patients who have received previous investigational agents or biologic therapies are eligible for enrollment. At least 30 days or 5 half-lives must have elapsed since receiving medical therapy directed at any NF1 related tumor. Patients who received prior medical therapy for a NF1 related tumor manifestation must have recovered from the acute toxic effects of all prior therapy to grade 1 CTCAEv5 except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment before entering this study. Chemotherapy agents: Patients who received chemotherapy must have recovered (CTCAE Grade <=1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 28 days is required between last chemotherapy dose and enrollment (provided the patient did not receive radiotherapy). Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. Patients who have received previous radiation therapy are eligible for enrollment. At least 6 weeks must have elapsed since the last radiation therapy and start of treatment. The only target ANF cannot have received radiation previously. At least 28 days must have elapsed since any major surgeries, with evidence of good wound healing. Minimally invasive biopsies and central line placements are not considered major surgeries. Patients who have received prior treatment with abemaciclib or another specific CDK4/6 inhibitor are not eligible for enrollment Adequate performance scale (Lansky/Karnofsky >=70%). Adequate organ function as defined below: Hematologic Function: Patients must have an absolute neutrophil count >= 1500/mililiters, hemoglobin >= 9 g/dL (transfusion independent, defined as not receiving blood transfusion unless related to trauma or surgeries), and platelets less than or equal to 100,000/mililiters (transfusion independent, defined as not receiving platelet transfusions unless related to trauma or surgeries) Hepatic Function: Patients must have bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST/ALT within <= 3 x upper limit of normal. Renal Function: Patients must have a creatinine clearance or radioisotope GFR >=60ml/min/1.73 m^2 or a normal serum creatinine based on age, described below. Age (years) is >12 and <=15 then Maximum Serum Creatinine (mg/dL) = 1.2 Age (years) is >15 then Maximum Serum Creatinine (mg/dL) = 1.5 Cardiac Function: Normal ejection fraction (ECHO or cardiac MRI) >= 53% (or the institutional normal; if a range is given then the upper value of the range will be used); QTC or QTcF <=450 msec. Willingness to avoid grapefruit or grapefruit juice during abemaciclib administration Informed Consent: Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. All patients or their legal guardians (if the patient is < 18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions. Based on animal studies, the effects of abemaciclib can cause fetal harm. For these reasons, women of child-bearing potential and men must agree to use a highly effective contraceptive method during treatment and for at least 3 months after the last dose of abemaciclib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of abemaciclib administration Woman subjects of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Contraceptive methods may include intrauterine devices (IUD), or barrier method, a spermicidal agent should be added as a double barrier protection; abstinence is also acceptable. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation she must discontinue treatment immediately. Data on fetal outcomes and breastfeeding are to be collected for regulatory reporting and drug safety evaluation. EXCLUSION CRITERIA: Pregnant women, or women who intend to become pregnant during the study, are excluded from this study because of the teratogenic effects of abemaciclib. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. May not have a NF1-related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy or surgery. Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel that would preclude adequate absorption, or preexisting Crohn s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea). Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses or renal transplant, or psychiatric illness/social situations that would limit compliance with study requirements. Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Patients with HIV who have adequate CD4 counts and who have no requirement for antiviral therapy will be eligible. NOTE: Screening is not required for enrollment. Patients with interstitial lung disease Requires treatment with strong CYP3A inhibitors or inducers Inability to swallow tablets, since tablets cannot be crushed or broken. Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol (see Study Procedure Manual). Prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target ANF on MRI. Refractory nausea and vomiting that would limit drug administration in the opinion of the Principal Investigator Known severe hypersensitivity to abemaciclib or any excipient of abemaciclib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib Clinical judgment by the investigator that the patient should not participate in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda M Carbonell
Phone
(240) 760-6006
Email
amanda.carbonell@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea M Gross, M.D.
Phone
(240) 858-3853
Email
andrea.gross@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea M Gross, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
Phone
888-624-1937

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
IPD Sharing Time Frame
Clinical data will be available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
IPD Sharing Access Criteria
Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2021-C-0011.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Cyclin-Dependent Kinase (CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type I (NF1) Related Atypical Neurofibromas

We'll reach out to this number within 24 hrs