Clinical trial: NCT01134601
Section: Duration of Study Involvement
Subsections: How Many People Will Take Part In This Study?

About 12 people will take part in this study. At the beginning of the study, patients will be treated with lower doses of the investigational drug. If the drug does not cause bad side effects, the dose will slowly be made higher as new patients take part in the study. The dose of AZD6244 will stay the same over the entire treatment for each patient. All patients will receive similar doses of radiation and capecitabine, a type of chemotherapy drug commonly used in the treatment of rectal cancer. A total of 18 patients are the most that would be able to enter the study.
Clinical trial: NCT01134601
Section: Participant's Rights
Subsections: Research Subject'S Rights

What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy:
- You will receive all treatment on this study at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH. Any medicine used as part of the study (AZD6244 and capecitabine) and medicines used to treat side effects of the study will be provided at no charge to you.  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs even if they are not covered by your insurance company.  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.  
The National Cancer Institute and the Pharmaceutical Company (Astra-Zeneca) that makes AZD6244 may inspect and copy patient's research records for quality assurance and data analysis.
Clinical trial: NCT01134601
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Rare But Serious:|The Most **Common Side Effects Of Capecitabine Are:**|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking the AZD6244. In some cases, side effects can be serious, long lasting, or may never go away.  
What side effects or risks can I expect from being in this study? Possible side effects from AZD6244: Likely:
- Diarrhea - Nausea or the urge to vomit
- Vomiting - Swelling of the arms and/or legs  
STUDY NUMBER: 10-C-0132 CONTINUATION: page 5 of 10 pages
- Fatigue or tiredness - Acne
- Skin rash with the presence of macules (flat discolored area) and papules (raised bump)
Less Likely:  
  
- Lack of enough red blood cells (anemia) - Belly pain
- Constipation
- Dry mouth
- Irritation or sores in the lining of the mouth
- Swelling of the face
- Fever - Increased blood level of a liver enzyme (ALT/SGPT)
- Increased blood level of a liver or bone enzyme (alkaline phosphatase)
- Increased blood level of a liver enzyme (AST/SGOT)
- Decreased number of a type of blood cell that helps to clot blood (platelet) - Loss of appetite
- Decreased levels of a blood protein called albumin
- Decreased blood level of magnesium
- Dizziness (or sensation of lightheadedness, unsteadiness, or giddiness) - Headache or head pain - Difficulty sleeping or falling asleep
- Cough
- Shortness of breath
- Dry skin
- Itching - High blood pressure

- Fever associated with dangerously low levels of a type of white blood cell (neutrophils) - Decrease in heart's ability to pump blood during the "active" phase of the heartbeat (systole)
Capeciatabine and radiation are not experimental treatments for rectal cancer. The possible side effects of capecitabine are listed below. Your doctor will discuss these with you. It is important to let your doctor know if you develop these side effects because adjustments to your treatment may need to be made.

Diarrhea Nausea and/or vomiting Sores in the mouth and throat (stomatitis) Upset stomach Loss of appetite Fatigue Too much water loss from the body (dehydration) Painful tingling rash on the hands and feet NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study STUDY NUMBER: 10-C-0132 CONTINUATION: page 6 of 10 pages Other types of rash Decrease in blood counts (especially white blood cell count) Itchy skin Hair loss Nail problems Tiredness or weakness Headache Fever Pain Trouble sleeping Changes in taste Pain (muscle, back, joint, chest)
Some additional aide effects may occur with radiation to the pelvic area. These side effects are listed below. Your doctor will discuss these with you. It is important to let your doctor know if you develop these side effects because changes may need to be made to your treatment. The short term side effects of radiation tend to go away a few weeks after treatment is completed.  
Likely short term side effects of radiation  
 Skin irritation in the area radiated (pelvis) Fatigue Diarrhea Hair loss in the area treated with radiation Less Likely **short term side effects of radiation.**
Burning with urination or urgent urination Decrease in blood counts Pain in the pelvis area Some side effects of radiation can happen many months or years after treatment. It is impossible to predict who will develop long term side effects. Your doctor will discuss these risks with you. The possible long term side effects of radiation to the pelvis can include:
Common: increased tendency to develop gas or diarrhea, more frequent or urgent bowel movements, infertility Uncommon: bleeding from the rectum, bleeding from the bladder, scarring of the vagina in females, decreased sexual function in males Extremely rare: injury to the hips that could result in a fracture of bone, life threatening tumor caused by radiation.

The aim of this study is to see if AZD6244 in combination with radiation and chemotherapy will cause your tumor to shrink. We hope that you will get personal medical benefit from taking part in this study, but we cannot be certain.  
These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the  
STUDY NUMBER: 10-C-0132 CONTINUATION: page 7 of 10 pages future who have cancer. While doctors hope AZD6244 will be more useful against cancer compared to the usual treatment, there is no proof of this yet. We do know that the information from this study will help doctors learn more about AZD6244 as a treatment for cancer. This information could help future cancer patients.
Clinical trial: NCT01134601
Section: Procedures
Subsections: What Does This Study Involve? Standard Of Care Treatment:

Treatments covered under this study may include capecitabine (a chemotherapy) and radiation to treat your cancer. These treatments will not be experimental. Your doctors will describe your treatment plan to you in detail before asking you to sign this consent form. You may be asked to sign a separate consent form for any treatment procedures not outlined in this consent.
Clinical trial: NCT01134601
Section: Purpose of Research
Subsections: Why Are You Being Asked To Take Part In This Study?

You are being asked to take part in this study because you have rectal cancer that has spread outside the inner wall of the rectum or into lymph nodes in the pelvis that typically would require radiation and chemotherapy for treatment. You are being asked to participate because we are studying if AZD6244 can be delivered with chemotherapy and radiation for patients with the type for tumor that you have.
Clinical trial: NCT01134601
Section: Withdrawal from Study
Subsections: Stopping Therapy

Your doctor may decide to stop your therapy for the following reasons:
- if he/she believes that it is in your best interest - if your disease grows during treatment - if you have side effects from the treatment that your doctor thinks are too severe
- if new information shows that another treatment would be better for you In this case, you will be informed of the reason therapy is being stopped. If the investigational treatment is stopped, you may continue to receive chemotherapy and radiation to complete your treatment if the investigator thinks it is safe.  
You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first.