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

This study is not yet open for participant recruitment.
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Verified April 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02961374
First received: November 10, 2016
Last updated: April 20, 2017
Last verified: April 2017
November 10, 2016
April 20, 2017
July 31, 2017
June 1, 2019   (Final data collection date for primary outcome measure)
  • Incidence of grade 2/3 adverse event (AE) rate assessed according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 2.5 years ]
  • Mean percent change in duodenal polyp burden assessed by EGD [ Time Frame: Baseline to 6 months post-intervention ]
    For all measurements of response, the 95% confidence intervals will be provided.
Same as current
Complete list of historical versions of study NCT02961374 on ClinicalTrials.gov Archive Site
  • Absolute and percent change in desmoid tumor size [ Time Frame: Baseline to 2.5 years ]
    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 ex
  • Absolute and percent change in duodenal polyp number [ Time Frame: Baseline to 6 months ]
    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 ex
  • Absolute and percent changes in lower gastrointestinal polyp burden [ Time Frame: Baseline to 2.5 years ]
    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 ex
  • Absolute and percent changes in number for the subset of participants with IPAA or ileo-rectal anastomosis with rectal stump [ Time Frame: Baseline to 2.5 years ]
    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 ex
  • Change in differentially expressed genes of duodenal polyps and uninvolved tissue [ Time Frame: Baseline to 2.5 years ]
    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 ex
  • EGFR and Wnt gene expression [ Time Frame: Up to 2.5 years ]
    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 ex
  • Immune response signaling in duodenal adenomas and uninvolved tissue [ Time Frame: Up to 2.5 years ]
    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 ex
  • Incidence of all adverse events assessed according to NCI CTCAE version 4.0 [ Time Frame: Up to 2.5 years ]
    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 and severity of adverse events will be tabulated and summarized across all grades. Grade 2+ adverse events will be similarly described and summarized separately. Overall toxicity incidence, as well as toxicity profiles will be explored and summarized.
Same as current
Not Provided
Not Provided
 
Erlotinib Hydrochloride in Reducing Duodenal Polyp Burden in Patients With Familial Adenomatous Polyposis at Risk of Developing Colon Cancer
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.

PRIMARY OBJECTIVES:

I. 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:

I. 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.

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

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

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

VIII. 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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Prevention
  • Attenuated Familial Adenomatous Polyposis
  • Familial Adenomatous Polyposis
  • Drug: Erlotinib Hydrochloride
    Given PO
    Other Names:
    • Cp-358,774
    • OSI-774
    • Tarceva
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Treatment (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO once weekly. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Erlotinib Hydrochloride
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
70
June 1, 2019
June 1, 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • Spigelman 2-3
  • 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
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness 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
  • Willingness to discontinue smoking for the duration of study intervention
  • 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 within institutional limits of normal
  • Urinary protein and urinary casts within institutional limits of normal
  • Not pregnant or breast feeding; 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
  • Willingness to use adequate contraception to avoid pregnancy or impregnation until 2 weeks after discontinuing study agent
  • Willingness to provide mandatory biospecimens as specified in the protocol

Exclusion Criteria:

  • 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, such as ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice
  • Use of CYP3A4 inducers such as rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's wort
  • Use of any other investigational agents =< 12 weeks prior to pre-registration
  • 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
  • Use of anticoagulation medications, including but not limited to coumadin, warfarin, plavix
  • 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 discontinue for the duration of clinical trial participation may be enrolled; an alternate drug to control gastroesophageal reflux disease (GERD)/peptic ulcer disease (PUD) symptoms will be suggested
  • 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
Sexes Eligible for Study: All
18 Years to 69 Years   (Adult, Senior)
No
Puerto Rico,   United States
 
 
NCT02961374
NCI-2016-01674
NCI-2016-01674 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00042
MAY2016-07-01 ( Other Identifier: Mayo Clinic )
MAY2016-07-01 ( Other Identifier: DCP )
N01CN00042 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Niloy Samadder Mayo Clinic
National Cancer Institute (NCI)
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP