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NCT01981551

Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis

Completed Phase 2 Results posted Last updated 6 February 2024
What this trial tests

Phase 2 trial testing PF-03084014 in Desmoid Tumors in 17 participants. Completed in 1 December 2023.

Timeline
31 October 2013
Primary endpoint
30 December 2018
1 December 2023

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment17
Start date31 October 2013
Primary completion30 December 2018
Estimated completion1 December 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 120, any sex, with Desmoid Tumors or Aggressive Fibromatosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With a Complete Response (CR) + Partial Response (PR) Primary · 20 months

Complete Response + Partial Response was determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if tha

Complete Response
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis0
Partial Response
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis5
Not Evaluable
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis1
Stable Disease
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis11
Progressive Disease
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis0
Number of Participants With Serious and Non-serious Adverse Events Secondary · Date treatment consent signed to date off study, approximately 66 months and 27 days.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one o

GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis17
Number of Participants With Somatic or Germline Mutations Identified in Adenomatous Polyposis Coli Gene (APC) or Catenin Beta-1 (CTNNB1) Genes Secondary · Baseline

Tumor and blood samples were obtained from participants and genotyped for somatic and germline mutations.

GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis15
Mean MD Anderson Symptom Inventory Scores After Treatment Secondary · At baseline prior to drug administration and at least every 6 cycles of drug (18 weeks) up to 20 months of treatment.

The MD Anderson Symptoms Inventory (MDSAI) questionnaire includes questions regarding 13 symptoms commonly experienced by patients with cancer and 6 additional items that assess the extent to which these symptoms interfered with how patients felt and were able to function. The 0-10 scale (0=none, 1-4=mild, 5-6=moderate, and 7-10=severe) assesses how patients felt and were able to function over the previous 24 hours. A component score representing symptom severity is obtained by taking the average of the 13 symptom items (e.g., pain, fatigue, etc.) together. A component score representing sympt

Symptom Severity Score
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis1.37± 1.46
Symptom Interference Score
GroupValue95% CI
PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis1.57± 2.69

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 66 months and 27 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-03084014 in Desmoid Tumors/Aggressive Fibromatosis
Serious: 9/17 (53%)
Deaths: 1/17

Serious adverse events (13 terms)

ReactionSystemPF-03084014 in Desmoid Tum…
Allergic reactionImmune system disorders
Back painMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
BronchospasmRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
FeverGeneral disorders
HematomaVascular disorders
HematuriaRenal and urinary disorders
Injury, poisoning and procedural complications - Other, specifyInjury, poisoning and procedural complications
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
StrokeNervous system disorders
Surgical and medical procedures - Other, hysterectomySurgical and medical procedures
Vaginal inflammationReproductive system and breast disorders
Other adverse events (217 terms — click to expand)

ReactionSystemPF-03084014 in Desmoid Tum…
DiarrheaGastrointestinal disorders
HeadacheNervous system disorders
HypophosphatemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Hot flashesVascular disorders
HyponatremiaMetabolism and nutrition disorders
PainGeneral disorders
Dry mouthGastrointestinal disorders
HypertensionVascular disorders
Rash acneiformSkin and subcutaneous tissue disorders
Skin infectionInfections and infestations
White blood cell decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
FeverGeneral disorders
Flu like symptomsGeneral disorders
Mucositis oralGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
Alkaline phosphatase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
BruisingInjury, poisoning and procedural complications
ConstipationGastrointestinal disorders
HypoalbuminemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Upper respiratory infectionRespiratory, thoracic and mediastinal disorders
Activated partial thromboplastin time prolongedInvestigations
ChillsGeneral disorders
DizzinessNervous system disorders
Dry skinSkin and subcutaneous tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Allergic reaction, Back pain, Blood bilirubin increased, Bronchospasm, Constipation, Fever, Hematoma, Hematuria.

Data from ClinicalTrials.gov NCT01981551 adverse events section.

Sponsor's own 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 (CR)+Partial Response (PR)) of PF-03084014 in patients with desmoid tumors/aggressive 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 (HRQOL)/symptom questionnaires will be administered at baseline and at each Clinical Center visit

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting cancer stem cell pathways for cancer therapy.
    Yang L, Shi P, Zhao G, Xu J, et al · · 2020 · cited 1354× · PMID 32296030 · DOI 10.1038/s41392-020-0110-5
  2. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update.
    Takebe N, Miele L, Harris PJ, Jeong W, et al · · 2015 · cited 1034× · PMID 25850553 · DOI 10.1038/nrclinonc.2015.61
  3. Notch signaling pathway: architecture, disease, and therapeutics.
    Zhou B, Lin W, Long Y, Yang Y, et al · · 2022 · cited 752× · PMID 35332121 · DOI 10.1038/s41392-022-00934-y
  4. Precision medicine for human cancers with Notch signaling dysregulation (Review).
    Katoh M, Katoh M. · · 2020 · cited 159× · PMID 31894255 · DOI 10.3892/ijmm.2019.4418
  5. Targeted therapy in cancer.
    Tsimberidou AM. · · 2015 · cited 156× · PMID 26391154 · DOI 10.1007/s00280-015-2861-1
  6. Clinical Activity of the γ-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors (Aggressive Fibromatosis).
    Kummar S, O'Sullivan Coyne G, Do KT, Turkbey B, et al · · 2017 · cited 137× · PMID 28350521 · DOI 10.1200/jco.2016.71.1994
  7. Targeting Signaling Pathways in Cancer Stem Cells for Cancer Treatment.
    Koury J, Zhong L, Hao J. · · 2017 · cited 99× · PMID 28356914 · DOI 10.1155/2017/2925869
  8. Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.
    Moore G, Annett S, McClements L, Robson T. · · 2020 · cited 85× · PMID 32575680 · DOI 10.3390/cells9061503

Verify or expand the search:

Other trials of PF-03084014

Trials testing the same drug.

Other recruiting trials for Desmoid Tumors

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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