Colon Cancer Clinical Trial

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

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. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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Full Description

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.

CORRELATIVE OBJECTIVES:

I. 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.

View Eligibility Criteria

Eligibility Criteria

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
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
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

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, 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

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

Study is for people with:

Colon Cancer

Phase:

Phase 2

Estimated Enrollment:

46

Study ID:

NCT02961374

Recruitment Status:

Completed

Sponsor:

National Cancer Institute (NCI)

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There are 8 Locations for this study

See Locations Near You

Mayo Clinic in Arizona
Scottsdale Arizona, 85259, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor Michigan, 48109, United States
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City Utah, 84112, United States
University of Puerto Rico
San Juan , 00936, Puerto Rico

How clear is this clinincal trial information?

Study is for people with:

Colon Cancer

Phase:

Phase 2

Estimated Enrollment:

46

Study ID:

NCT02961374

Recruitment Status:

Completed

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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