Ignite Creation Date:
2024-05-06 @ 2:09 AM
Last Modification Date:
2024-10-26 @ 11:14 AM
Study NCT ID:
NCT01981551
Status:
COMPLETED
Last Update Posted:
2024-02-06
First Post:
2013-10-31
Brief Title:
Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid TumorsAggressive Fibromatosis
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid TumorsAggressive Fibromatosis
Status:
COMPLETED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Desmoid tumors also known as aggressive fibromatosis are rare locally invasive slow-growing soft-tissue tumors The disease can be either asymptomatic or be associated with severe loss of organ function and significant morbidity
Treatment with the selective small-molecule Gamma-secretase inhibitor PF-03084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early phase clinical trial
The Notch pathway is a key regulator of cell differentiation proliferation and apoptosis aberrant signaling via the Notch pathway is associated with carcinogenesis
Objectives
Primary Determine the response rate Complete Response CRPartial Response PR of PF-03084014 in patients with desmoid tumorsaggressive fibromatosis
Secondary Assess symptom measures at baseline and on study perform genotyping for germline and somatic mutations in adenomatous polyposis coli gene APC and catenin-beta 1 CTNNB1 genes correlate clinical response to therapy with genotyping data and assess modulation of the Notch pathway by evaluating notch response genes in tumor biopsies at baseline and after drug administration
Eligibility
Age greater than or equal to18 histologically confirmed desmoid tumor not amenable to curative resection or definitive radiation therapy that has progressed after receiving at least one line of standard treatment adequate organ function
Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies
Study Design
This is an open-label Phase II trial of PF-03084014 study drug will be administered orally at 150 mg twice a day in 21-day cycles
Optional tumor biopsies for research purposes will be performed at baseline prior to study treatment and at the beginning of cycle 7 - one cycle
Restaging scans magnetic resonance imaging MRI with diffusion weighting will be performed at baseline at the end of cycles 1 and 6 and then every 6 cycles
Health-related quality of life HRQOLsymptom questionnaires will be administered at baseline and at each Clinical Center visit
Desmoid tumors also known as aggressive fibromatosis are rare locally invasive slow-growing soft-tissue tumors The disease can be either asymptomatic or be associated with severe loss of organ function and significant morbidity
Treatment with the selective small-molecule Gamma-secretase inhibitor PF-03084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early phase clinical trial
The Notch pathway is a key regulator of cell differentiation proliferation and apoptosis aberrant signaling via the Notch pathway is associated with carcinogenesis
Objectives
Primary Determine the response rate Complete Response CRPartial Response PR of PF-03084014 in patients with desmoid tumorsaggressive fibromatosis
Secondary Assess symptom measures at baseline and on study perform genotyping for germline and somatic mutations in adenomatous polyposis coli gene APC and catenin-beta 1 CTNNB1 genes correlate clinical response to therapy with genotyping data and assess modulation of the Notch pathway by evaluating notch response genes in tumor biopsies at baseline and after drug administration
Eligibility
Age greater than or equal to18 histologically confirmed desmoid tumor not amenable to curative resection or definitive radiation therapy that has progressed after receiving at least one line of standard treatment adequate organ function
Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies
Study Design
This is an open-label Phase II trial of PF-03084014 study drug will be administered orally at 150 mg twice a day in 21-day cycles
Optional tumor biopsies for research purposes will be performed at baseline prior to study treatment and at the beginning of cycle 7 - one cycle
Restaging scans magnetic resonance imaging MRI with diffusion weighting will be performed at baseline at the end of cycles 1 and 6 and then every 6 cycles
Health-related quality of life HRQOLsymptom questionnaires will be administered at baseline and at each Clinical Center visit
Detailed Description:
Background
Desmoid tumors also known as aggressive fibromatosis are rare locally invasive slow-growing soft-tissue tumors The disease can be either asymptomatic or be associated with severe loss of organ function and significant morbidity
Treatment with the selective small-molecule Gamma-secretase inhibitor PF-03084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early phase clinical trial
The Notch pathway is a key regulator of cell differentiation proliferation and apoptosis aberrant signaling via the Notch pathway is associated with carcinogenesis
Objectives
Primary Determine the response rate Complete Response CRPartial Response PR of PF-03084014 in patients with desmoid tumorsaggressive fibromatosis
Exploratory Assess symptom measures at baseline and on study perform genotyping for germline and somatic mutations in adenomatous polyposis coli gene APC and catenin-beta 1 CTNNB1 genes correlate clinical response to therapy with genotyping data and assess modulation of the Notch pathway by evaluating notch response genes in tumor biopsies at baseline and after drug administration
Eligibility
Age greater than or equal to18 histologically confirmed desmoid tumor not amenable to curative resection or definitive radiation therapy that has progressed after receiving at least one line of standard treatment adequate organ function
Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies
Study Design
This is an open-label Phase II trial of PF-03084014 study drug will be administered orally at 150 mg twice a day in 21-day cycles
Optional tumor biopsies for research purposes will be performed at baseline prior to study treatment and at the beginning of cycle 7 - one cycle
Restaging scans computed tomography CT scan of the known site of disease will be performed at baseline and then every 6 cycles - one cycle
Optional magnetic resonance imaging MRI scans may be performed prior to start of study treatment end of cycle 1 and every 6 cycles at the same times as the CT scans
Health-related quality of life HRQOLsymptom questionnaires will be administered at baseline and at restaging
Desmoid tumors also known as aggressive fibromatosis are rare locally invasive slow-growing soft-tissue tumors The disease can be either asymptomatic or be associated with severe loss of organ function and significant morbidity
Treatment with the selective small-molecule Gamma-secretase inhibitor PF-03084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early phase clinical trial
The Notch pathway is a key regulator of cell differentiation proliferation and apoptosis aberrant signaling via the Notch pathway is associated with carcinogenesis
Objectives
Primary Determine the response rate Complete Response CRPartial Response PR of PF-03084014 in patients with desmoid tumorsaggressive fibromatosis
Exploratory Assess symptom measures at baseline and on study perform genotyping for germline and somatic mutations in adenomatous polyposis coli gene APC and catenin-beta 1 CTNNB1 genes correlate clinical response to therapy with genotyping data and assess modulation of the Notch pathway by evaluating notch response genes in tumor biopsies at baseline and after drug administration
Eligibility
Age greater than or equal to18 histologically confirmed desmoid tumor not amenable to curative resection or definitive radiation therapy that has progressed after receiving at least one line of standard treatment adequate organ function
Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies
Study Design
This is an open-label Phase II trial of PF-03084014 study drug will be administered orally at 150 mg twice a day in 21-day cycles
Optional tumor biopsies for research purposes will be performed at baseline prior to study treatment and at the beginning of cycle 7 - one cycle
Restaging scans computed tomography CT scan of the known site of disease will be performed at baseline and then every 6 cycles - one cycle
Optional magnetic resonance imaging MRI scans may be performed prior to start of study treatment end of cycle 1 and every 6 cycles at the same times as the CT scans
Health-related quality of life HRQOLsymptom questionnaires will be administered at baseline and at restaging
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 14-C-0007 | None | None | None |