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Desmoid TumorsPhase 2NCT01981551

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

A Phase 2 study testing PF-03084014 in people with Desmoid Tumors and Aggressive Fibromatosis, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Desmoid Tumors, Aggressive Fibromatosis
What is being tested?
PF-03084014
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
31 Oct 2013to 1 Dec 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 2.1.1.1 Patients must have histologically confirmed desmoid tumor confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), that has progressed after receiving at least one line of standard treatment and that is not amenable to surgical resection or definitive radiation therapy.
  • 2.1.1.2 Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies.
  • 2.1.1.3 Any line of therapy with prior desmoid therapy, including radiotherapy, should have been completed at least 2 weeks before study entry and all toxicities must have resolved at least to eligibility levels.
  • 2.1.1.4 Age greater than or equal 18 years; because no dosing or adverse event data are currently available on the use of PF-03084014 in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
  • 2.1.1.5 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal 2.
  • 2.1.1.6 Life expectancy > 3 months.
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  • 2.1.1.7 Patients must have normal organ and marrow function as defined below:
  • -absolute neutrophil count greater than or equal 1,500/mcL
  • -platelets greater than or equal 100,000/mcL
  • -total bilirubin less than or equal 1.5 times institutional upper limit of normal
  • -Aspartate aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/Alanine aminotransferase (ALT) Serum glutamic-pyruvic transaminase (SGPT) less than or equal 5 times institutional upper limit of normal
  • -creatinine < 1.5 times institutional upper limit of normal
  • OR
  • -creatinine clearance greater than or equal 60 mL/min/1.73 m(2) for patients with creatinine levels >1.5 mg/dL
  • -hemoglobin greater than or equal 9 g/dL
  • 2.1.1.8 Patients must be able to swallow whole tablets or capsules with no gastrointestinal (GI) condition affecting absorption; nasogastric or G-tube administration is not allowed.
  • 2.1.1.9 The effects of PF-03084014 on the developing human fetus are unknown. For this reason and because >=-secretase inhibitors are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for at least 6 months after dosing with study drugs ceases. 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 for the duration of study participation, and 6 months after completion of study drug administration.
  • 2.1.1.10 Ability to understand and the willingness to sign a written informed consent document.
  • 2.1.1.11 Evidence of measurable disease by computed tomography (CT) scan. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal 20 mm by chest x-ray, as greater than or equal 10 mm with CT scan, or greater than or equal 10 mm with calipers by clinical exam.

Who cannot join

  • 2.1.2.1 Patients who are receiving any other investigational agents. Concurrent mediations that the patient is taking will be reviewed by the principal investigator (PI) to assess safety and eligibility.
  • 2.1.2.2 Prior treatment with Gamma-secretase inhibitors or anti-notch antibody therapy.
  • 2.1.2.3 Uncontrolled intercurrent illness including, but not limited to, serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • 2.1.2.4 Corrected QT interval (QTc) interval of >470 msec at study entry; congenital long QT syndrome.
  • 2.1.2.5 Pregnant women are excluded from this study because PF-03084014 is a Gamma-secretase inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PF-03084014, breastfeeding should be discontinued if the mother is treated with PF-03084014.
  • 2.1.2.6 Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow the tablet whole. Tablets must not be crushed or chewed; nasogastric or gastrostomy (G)-tube administration is not allowed.
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  • 2.1.2.7 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with PF-03084014.
  • 2.1.3 Recruitment Strategies
  • We have had multiple discussions with the Desmoid Tumor Research Foundation, Inc., who have various outreach efforts including patient meetings and webcasts. Senior executives of the Foundation have indicated strong interest in this trial and willingness to inform their members. We also have a network of referring physicians nationally that refers patients with solid tumors to our clinical program. Given our interest and trials for sarcomas, we have formed connections with centers that treat patients with mesenchymal malignancies. We will be informing all of these of the availability of this trial once it is open.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.
Read more

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
Read the 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 (CR)+Partial Response (PR)) of PF-03084014 in patients with desmoid tumors/aggressive 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 (HRQOL)/symptom questionnaires will be administered at baseline and at restaging
Being tested
PF-03084014
Keywords
Desmoid Tumor, Aggressive Fibromatosis, Gamma-secretase Inhibitor, Notch Pathway
Medical subject headings
Desmoid Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-03084014Drug

    Treatment with the selective small-molecule >=-secretase inhibitor PF- 3084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early-phase clinical trial.

Study groups in NCT01981551
Study groupRoleWhat they receive
PF-03084014 in Desmoid Tumors/Aggressive FibromatosisExperimentalPF-03084014 will be administered orally at 150 mg twice a day in 21-day cycles
Receives: Drug: PF-03084014

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With a Complete Response (CR) + Partial Response (PR)

    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 that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: 20 months

Secondary outcomes (3)

  1. Number of Participants With Serious and Non-serious Adverse Events

    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 of the previous outcomes mentioned.

    Measured: Date treatment consent signed to date off study, approximately 66 months and 27 days.

  2. Number of Participants With Somatic or Germline Mutations Identified in Adenomatous Polyposis Coli Gene (APC) or Catenin Beta-1 (CTNNB1) Genes

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

    Measured: Baseline

  3. Mean MD Anderson Symptom Inventory Scores After 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 symptom distress is obtaining by averaging the 6 symptom interference items (e.g., general activity, mood, etc.).

    Measured: At baseline prior to drug administration and at least every 6 cycles of drug (18 weeks) up to 20 months of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2013 (estimated)
  2. Study start31 Oct 2013
  3. Primary completion30 Dec 2018
  4. Study completion1 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01981551
Sponsor's protocol ID
140007
Other IDs
14-C-0007
Status last verified
Jan 2024
First submitted
31 Oct 2013
Last updated
6 Feb 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Publications

  • de Bree E, Keus R, Melissas J, Tsiftsis D, van Coevorden F. Desmoid tumors: need for an individualized approach. Expert Rev Anticancer Ther. 2009 Apr;9(4):525-35. doi: 10.1586/era.09.9.

    PubMed 19374605

  • Lev D, Kotilingam D, Wei C, Ballo MT, Zagars GK, Pisters PW, Lazar AA, Patel SR, Benjamin RS, Pollock RE. Optimizing treatment of desmoid tumors. J Clin Oncol. 2007 May 1;25(13):1785-91. doi: 10.1200/JCO.2006.10.5015.

    PubMed 17470870

  • Lewis JJ, Boland PJ, Leung DH, Woodruff JM, Brennan MF. The enigma of desmoid tumors. Ann Surg. 1999 Jun;229(6):866-72; discussion 872-3. doi: 10.1097/00000658-199906000-00014.

    PubMed 10363901

  • Kummar S, O'Sullivan Coyne G, Do KT, Turkbey B, Meltzer PS, Polley E, Choyke PL, Meehan R, Vilimas R, Horneffer Y, Juwara L, Lih A, Choudhary A, Mitchell SA, Helman LJ, Doroshow JH, Chen AP. Clinical Activity of the gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors (Aggressive Fibromatosis). J Clin Oncol. 2017 May 10;35(14):1561-1569. doi: 10.1200/JCO.2016.71.1994. Epub 2017 Mar 28.

    PubMed 28350521

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PF-03084014 in people with Desmoid Tumors and Aggressive Fibromatosis, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Complete Response (CR) + Partial Response (PR) (time frame: 20 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01981551, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.

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