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Attenuated Familial Adenomatous PolyposisPhase 2NCT02961374

Erlotinib Hydrochloride in Reducing Duodenal Polyp Burden in Patients With Familial Adenomatous Polyposis at Risk of Developing Colon Cancer

A Phase 2 study testing Erlotinib and Erlotinib Hydrochloride in people with Attenuated Familial Adenomatous Polyposis and Familial Adenomatous Polyposis, run by National Cancer Institute (NCI) at 8 sites in 2 countries.

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

This phase II trial studies the side effects of erlotinib hydrochloride and how well it works in reducing duodenal polyp burden in patients with familial adenomatous polyposis at risk of developing colon cancer. Read more about this study

Who is it for?
Ages 18 to 69 years
What is being tested?
Erlotinib and Erlotinib Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
8 sitesin 2 countries
Study dates
27 Oct 2017to 27 Sep 2021
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 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRE-REGISTRATION INCLUSION
  • Diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), defined as at least one of the following:
  • Genetic diagnosis with confirmed APC mutation (Clinical Laboratory Improvement Act [CLIA] certified lab or research testing)
  • Obligate carrier
  • Clinical diagnosis of classic FAP with >= 100 colorectal adenomas status post colectomy and a family history of FAP
  • Clinical diagnosis of FAP, based on personal and family history; Note: This criterion requires documented review and agreement from either the study chair or the Cancer Prevention Network (CPN) lead investigator
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  • Ability to understand and the willingness to sign a written informed consent document
  • Willing to discontinue taking nonsteroidal anti-inflammatory drugs (NSAIDS) for 30 days prior to initiation of and during intervention; exception: use of =< 81 mg daily or =< 650 mg weekly aspirin is allowed
  • Willing to discontinue smoking for the duration of study intervention
  • Willing to provide mandatory biospecimens as specified in the protocol
  • REGISTRATION INCLUSION
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Leukocytes (white blood cells [WBC]) >= 3,000/uL (>= 2,500/uL for African-American participants)
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 11.5 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Alkaline phosphatase =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) =< 2 x institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2 x institutional upper limit of normal (ULN)
  • Creatinine =< institutional upper limits of normal (ULN)
  • Urinary testing results within institutional limits of normal or deemed clinically insignificant
  • Spigelman 2-3
  • Not pregnant or breast feeding; Note: the effects of erlotinib (Tarceva ) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; breastfeeding should be discontinued if the mother is treated with erlotinib
  • Willing to use adequate contraception to avoid pregnancy or impregnation until 2 weeks after discontinuing study agent

Who cannot join

  • PRE-REGISTRATION EXCLUSION
  • Any prior treatment with erlotinib or other agent whose primary mechanism of action is known to inhibit EGFR
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib
  • Use of potent CYP3A4 inhibitors, including but not limited to ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice
  • Use of potent CYP3A4 inducers, including but not limited to rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's wort
  • Use of any other investigational agents =< 12 weeks prior to pre-registration
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  • Uncontrolled intercurrent illness or recent surgical procedure that in the opinion of the investigative team would limit compliance with study requirements, including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Myocardial infarction =< 6 months prior to intervention
  • Severely impaired lung function
  • Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with study intervention
  • Diagnosed liver disease, such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations
  • History of invasive malignancy =< 3 years prior to pre-registration; exception: adequately treated carcinoma of the cervix, carcinoma in situ, or basal or squamous cell carcinomas of the skin
  • Individuals on anticoagulation medications who cannot safely discontinue the medication for at least 48 hours prior to the study endoscopy, as determined by the study investigator and/or participant's primary healthcare provider
  • History of any upper gastrointestinal (GI) surgery that does not permit access to or evaluation of a 10 cm segment of the duodenum that includes the duodenal bulb, i.e. Whipple procedure or similar
  • REGISTRATION EXCLUSION
  • Histologically-confirmed high grade dysplasia (HGD), cancer, or polyp burden that is not quantifiable
  • Regular (>= 2 times per week) use of drugs that alter the pH of the gastrointestinal tract (GI) tract, such as proton pump inhibitors (PPI) and antacids; exceptions: individuals who use prescription PPIs and have approval from their primary health care provider to replace the PPI with an H2 receptor agonist, i.e. ranitidine, for the duration of the trial will be eligible
  • Gastrointestinal bleeding; note that the presence of any symptoms (dyspnea, fatigue, angina, weakness, malaise, melena, hematochezia, hematemesis, anemia, abdominal pain) will require clinical assessment to rule out gastrointestinal bleeding

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States7 sites
  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

Puerto Rico1 site
  • University of Puerto Rico

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: Phase II Trial of Weekly Erlotinib Dosing to Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis

This phase II trial studies the side effects of erlotinib hydrochloride and how well it works in reducing duodenal polyp burden in patients with familial adenomatous polyposis at risk of developing colon cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the mean percent change in duodenal polyp burden (sum of diameters from all polyps) from baseline to 6 months post-intervention for familial adenomatous polyposis (FAP) subjects receiving weekly erlotinib hydrochloride (erlotinib).

II. To assess the grade 2/3 adverse event rate in this population and compare it to historical data.

SECONDARY OBJECTIVES:

  1. To evaluate all adverse events at least possibly attributed to weekly erlotinib.

II. To assess the absolute and percent change in duodenal polyp number from baseline to 6 months.

III. To assess the absolute and percent changes in lower gastrointestinal polyp burden and number for the subset of participants with ileal pouch anal anastomosis (IPAA) or ileo-rectal anastomosis with rectal stump.

IV. To assess the absolute and percent change in desmoid tumor size in participants who have baseline and follow up computed tomography (CT)s performed as part of their standard of care.

CORRELATIVE OBJECTIVES:

  1. Gene expression profiles in duodenal adenomas and uninvolved tissue will be compared between baseline and endpoint samples using negative binomial statistics (DESeq2).

II. Identify differentially expressed genes between duodenal polyps and uninvolved tissue at endpoint compared to baseline.

III. Evaluate the effect of weekly erlotinib on EGFR and Wnt target gene expression in duodenal adenomas.

IV. Evaluate the effect of weekly erlotinib on immune response signaling in duodenal adenomas and uninvolved tissue.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Erlotinib, Erlotinib Hydrochloride
Medical subject headings
Attenuated familial adenomatous polyposis, Adenomatous Polyposis Coli

What participants receive

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

  • ErlotinibDrug

    Given PO

  • Erlotinib HydrochlorideDrug

    Also called Cp-358,774, OSI-774, Tarceva

    Given PO

Study groups in NCT02961374
Study groupRoleWhat they receive
Treatment (erlotinib hydrochloride)ExperimentalPatients receive erlotinib hydrochloride PO once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Erlotinib; Drug: Erlotinib Hydrochloride

What is being measured

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

  1. Mean Percent Change in Duodenal Polyp Burden

    Assessed by esophagogastroduodenoscopy, the mean percent change was calculated by subtracting the sum of diameters from all polyps at baseline from the sum of diameters of all polyps at 6 months, then dividing by the sum of diameters from all polyps at baseline and multiplying by 100.

    Measured: Baseline to 6 months post-intervention

  2. Number of Participants With Grade 2/3 Adverse Event (AE)

    Assessed according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of patients reporting a grade 2 or higher event are reported.

    Measured: Up to 7 months from registration

Secondary outcomes (7)
  1. Number of Participants With Any Adverse Events

    Assessed according to NCI CTCAE version 4.0. All registered and treated participants will be evaluable for AEs from the time of their first dose of weekly erlotinib treatment. To evaluate the AE profile for this treatment, the maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number of patients reporting a grade 1 or higher adverse event at least possibly related to treatment are reported.

    Measured: Up to 7 months from registration

  2. Change in Duodenal Polyp Number

    The number of duodenal polyps at baseline and the number of polyps remaining after 6 months of treatment will collected. The change in duodenal polyp number will be calculated for each patient by subtracting the baseline number of polyps from the 6 month number. Therefore a negative value indicates a decrease in the number of polyps present after 6 months. The median difference and standard deviation is reported.

    Measured: Baseline to 6 months

  3. Absolute Change in Lower Gastrointestinal Polyp Burden

    Lower GI polyp burden was defined using the Pouch Exam form as either 1) the average diameter reported for pouch for participants with ileal pouch-anal anastomosis (IPAA), or 2) the average diameter reported for rectum for participants with ileorectal anastomosis (IRA) + rectal stump. Absolute change from baseline to month 6 are reported here.

    Measured: Baseline to 6 months

  4. Percent Change in Lower Gastrointestinal Polyp Burden

    Lower GI polyp burden was defined using the Pouch Exam form as either 1) the average diameter reported for pouch for participants with ileal pouch-anal anastomosis (IPAA), or 2) the average diameter reported for rectum for participants with ileorectal anastomosis (IRA) + rectal stump. The percent change from baseline to month 6 are reported here.

    Measured: Baseline to 6 months

  5. Absolute Change in Lower Gastrointestinal Polyp Number

    Lower GI polyp number was defined using the Pouch Exam form as either 1) the number of polyps reported for pouch for participants with ileal pouch-anal anastomosis (IPAA), or 2) the number of polyps reported for rectum for participants with ileorectal anastomosis (IRA) + rectal stump. Absolute change from baseline to month 6 are reported here.

    Measured: Baseline to 6 months

  6. Percent Change in Lower Gastrointestinal Polyp Number

    Lower GI polyp number was defined using the Pouch Exam form as either 1) the number of polyps reported for pouch for participants with IPAA, or 2) the number of polyps reported for rectum for participants with IRA + rectal stump.

    Measured: Baseline to 6 months

  7. Absolute and Percent Change in Desmoid Tumor Size

    Laboratory measures will be correlated with participant outcomes (i.e., polyp burden, adverse events) and with each other as well. Cut-points will be determined based on previously defined and accepted standards. Descriptive statistics and simple scatter plots will be generated to review the tissue-based biomarker data. For continuous variables, the actual and % change in the level of each of the biomarkers from pre- to post-intervention will be explored using Wilcoxon signed rank tests, and paired sample t-tests. All categorical variables will be analyzed using chi-square tests or Fisher's exact test. For all translational endpoints, any notable statistical result will be viewed as an impetus for further study rather than as a definitive finding in and of itself.

    Measured: Baseline to 6 months

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 2016 (estimated)
  2. Study start27 Oct 2017
  3. Primary completion23 Feb 2020
  4. Study completion27 Sep 2021

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
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02961374
Sponsor's protocol ID
NCI-2016-01674
Other IDs
NCI-2016-01674, N01-CN-2012-00042, MAY2016-07-01, MAY2016-07-01, N01CN00042, P30CA015083
Status last verified
Jul 2022
First submitted
10 Nov 2016
Last updated
26 Jul 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer. 2023 Oct;22(4):413-422. doi: 10.1007/s10689-023-00334-3. Epub 2023 Apr 29.

    PubMed 37119510
  • Samadder NJ, Foster N, McMurray RP, Burke CA, Stoffel E, Kanth P, Das R, Cruz-Correa M, Vilar E, Mankaney G, Buttar N, Thirumurthi S, Turgeon DK, Sossenheimer M, Westover M, Richmond E, Umar A, Della'Zanna G, Rodriguez LM, Szabo E, Zahrieh D, Limburg PJ. Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis. Gut. 2023 Feb;72(2):256-263. doi: 10.1136/gutjnl-2021-326532. Epub 2022 May 30.

    PubMed 35636921

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erlotinib and Erlotinib Hydrochloride in people with Attenuated Familial Adenomatous Polyposis and Familial Adenomatous Polyposis, run by National Cancer Institute (NCI) at 8 sites in 2 countries.

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 24 inclusion and 23 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 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Puerto Rico. 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 22 Sep 2021). 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?

Mean Percent Change in Duodenal Polyp Burden (time frame: Baseline to 6 months post-intervention). The study lists 2 primary outcomes in all. 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 NCT02961374, which also lists 2 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 26 Jul 2022.

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