AZD6244 With Cetuximab for Solid Tumors and Colorectal Cancer

Completed · Phase 1

Conditions studied: Colonic Neoplasms, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer

In brief

Background: \- The experimental cancer treatment drug AZD6244 has been shown to block signals that tell cancer cells to grow. Cetuximab, a drug approved to treat cancer of the head, neck, colon, and rectum, also blocks signals that tell cancer cells to grow. Researchers are investigating the highest safe dose of AZD6244 to give with cetuximab, and will also investigate the effectiveness of this drug combination in individuals who have colorectal cancer that involves a particular protein known as the K-RAS protein. Cetuximab is not used to treat colorectal cancer with K-RAS tumors because it has not been shown to be effective, but researchers believe that adding AZD6244 to cetuximab may improve how well cetuximab works, even in people with K-RAS tumors. Objectives: * To evaluate the safety and effectiveness of AZD6244 in combination with cetuximab for solid tumors that have not responded to standard treatment. * To evaluate the safety and effectiveness of AZD6244 in combination with cetuximab for colorectal cancer that involves the K-RAS protein and has not responded to standard treatment. Eligibility: * Individuals at least 18 years of age who have been diagnosed with solid tumors that have not responded to standard treatment. * Individuals at least 18 years of age who have been diagnosed with colorectal cancer that has not responded to standard treatment. Design: * This protocol will involve two separate studies: an initial study to establish the highest safe and effective dose of AZD6244 and cetuximab in individuals with solid tumors, and an expansion study of AZD6244 and cetuximab in individuals with colorectal cancer involving the K-RAS protein. * Participants will be screened with a full medical history and physical examination, blood samples, imaging studies, and other tests as required by the researchers. * AZD6244 is a capsule to be swallowed once or twice a day, every day, with water on an empty stomach. Cetuximab will be given intravenously once a week, over 2 hours for the first dose and over an hour for every following dose. This combination of daily AZD6244 and weekly cetuximab will be repeated in 28-day cycles of treatment. Participants will keep a diary to record the time of taking AZD6244 each day, as well as any side effects. * Participants will have frequent blood tests and other exams during the first cycle of treatment, up to five visits to the National Institutes of Health (NIH) and other visits to their local doctor to in the first 28-day cycle. * During subsequent cycles, participants will have four visits to NIH and four visits to your local doctor for examinations, blood tests, and imaging studies. * Participants may continue to receive the AZD6244 with cetuximab for up to 6 cycles, until the tumor grows, unacceptable side effects development, or the participant or participant's doctor decides to stop participation. There will be a final study visit that repeats the procedures performed during the screening visit....

Key facts

Study ID: NCT01287130
Run by: National Cancer Institute (NCI)
People needed: 10
Starts: 2011-01-07
Expected to finish: 2013-08-27
Last updated by the study team: 2019-12-17

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients who have had chemotherapy, radiotherapy or hormonal therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (less than or equal to grade 1) from adverse events due to agents administered more than 4 weeks earlier.
Concurrent treatment with an investigational agent other than the investigational agent(s) used in this study OR treatment within 4 weeks of study entry with any investigational agent(s) or device(s).
Failure to recover fully (as judged by the investigator) from prior surgical procedures.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or other agents used in study.
Patients taking high doses (more than recommended daily dose) of vitamin E will be excluded. Patients can discontinue use of high dose vitamin E prior to study entry to be considered eligible.
Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain AZD6244 capsules.
Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, prior cardiomyopathy, LVEF less than 50%, unstable angina pectoris, cardiac arrhythmia (i.e. atrial fibrillation), or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because AZD6244 is a small molecule kinase 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 AZD6244, breastfeeding should be discontinued if the mother is treated with AZD6244. These potential risks may also apply to other agents used in this study.
HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Patients who are serologically positive for Hepatitis B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible.
Use of strong CYP1A2 or 3A4 inducers and/or inhibitors (for example, but not limited to, ketoconazole, rifampacin, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, grapefruit or grapefruit juice, ifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort) is not permitted while on study or within 7 days prior to study enrollment.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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