Phase II Study of Minocycline for Reducing Symptom Burden in Colorectal Patients

Nearly 40% of patients with colorectal cancer who receive oxaliplatin-based chemotherapy
experience neuropathy (nerve damage that can include numbness, pain, and/or loss of motor
function). Sometimes, this nerve damage is serious enough that the chemotherapy dose has to
be lowered or stopped completely. Researchers want to find out if taking minocycline can
lower the side effects caused by chemotherapy given to treat colorectal cancer.

Study Groups:

If you agree to take part in this study, you will be randomly assigned (as in the flip of a
coin) to 1 of 2 groups. You will have an equal chance of being in either group:

- If you are in Group 1, you will take a placebo.

- If you are in Group 2, you will take minocycline.

Neither you nor the study staff will know if you are receiving the study drug or the placebo.
However, if needed for your safety, the study staff will be able to find out what you are
receiving.

Study Drug Administration:

Starting on Day 1 of Cycle 1 of chemotherapy, you will start taking the study drug/placebo
capsule by mouth, twice a day every day.

You should take the study drug/placebo with a full glass (8 ounces) of water. You may take it
with or without food, but if it causes an upset stomach, you should take it with food.

You should not lie down for at least 30 minutes after taking the study drug/placebo to reduce
the risk of side effects.

Study Visits:

Before you start taking the study drug/placebo:

- You will complete 4 questionnaires about pain and other symptoms, and your quality of
life. You will also complete a questionnaire about your tobacco history. It should take
about 15-25 minutes to complete all questionnaires.

- You may complete a sensory test. For this test, researchers will try to find out how
sensitive you are to touching things such as small bumps on a board. This test will take
about 10 minutes to complete.

- If possible, blood (about 6 teaspoons) will be drawn to test for markers of
inflammation. Markers of inflammation are found in the blood and may be related to your
symptoms.

1 time each week:

- You will complete a questionnaire in the clinic or by telephone about any symptoms you
may be having and how they may be affecting your daily activities. The questionnaire
should take about 3-5 minutes to complete each time.

At each chemotherapy cycle:

- You will fill out 2 questionnaires in the clinic or by telephone about pain and other
symptoms. It should take about 10-15 minutes to complete the questionnaires.

- The study staff will make a count of the number of pills that you took so far. If you
are coming to the MD Anderson or Harris Health clinic, bring the study drug/placebo
container (along with any remaining drug/placebo).

At about 2 months:

- If you return to the MD Anderson or Harris Health clinic for this visit, the following
additional procedures will be performed:

- If possible, blood (about 6 teaspoons) will be drawn to test for markers of
inflammation.

You may complete a sensory test. This test will take about 10 minutes to complete.

End-of-Treatment Visit (at about 4 months):

- You will fill out the 4 questionnaires in the clinic or by telephone about your
symptoms. It should take about 15-20 minutes to complete all of the questionnaires.

- The study staff will make a count of the number of pills that you took so far.

If you return to the MD Anderson or Harris Health clinic for this visit:

- If possible, blood (about 6 teaspoons) will be drawn to test for markers of
inflammation.

- You may complete a sensory test. This test will take about 10 minutes to complete.

- You must bring the study drug/placebo container (along with any remaining drug/placebo).

Length of Study:

You may continue taking the study drug/placebo for up to 4 months, if there are no treatment
delays. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation in the study will be over at the End-of-Study visit.

End-of-Study Visit:

At about 6 months, the following tests and procedures will be performed:

°You will fill out 4 questionnaires in the clinic or by telephone about pain and other
symptoms and your quality of life. You will also complete a questionnaire about your tobacco
history. It should take about 15-25 minutes to complete all of the questionnaires.

If you return to the MD Anderson or Harris Health clinic for this visit:

- If possible, blood (about 6 teaspoons) will be drawn to test for markers of
inflammation.

- You may complete a sensory test. This test will take about 10 minutes to complete.

This is an investigational study. Minocycline is FDA approved and commercially available for
the treatment of bacterial infection. Its use in this study is investigational.

Up to 166 participants will be enrolled in this study. Up to 83 will be enrolled at the
Harris Health System.

Inclusion Criteria:

1. Patients with a pathologically proven diagnosis of CRC seen either at MD Anderson or
LBJ.

2. Patients > or = 18 years old.

3. Patients who qualify for oxaliplatin-based chemotherapy (in the adjuvant or metastatic
setting) and are likely to receive at least 3 months of oxaliplatin.

4. Patients who speak English or Spanish (due to language options for the MDASI version
being used in this study, we are only recruiting English-speaking or Spanish-speaking
patients).

5. Patients with an NCI-CTCv4 sensory neuropathy score of 0.

6. Patients with adequate renal function (serum creatinine must be < 1.5 times the upper
limit of the institutional normal range) and no prior renal disease that in the
opinion of the attending physician would make the patient ineligible to receive the
study drug . Test results must be no more than 3 months old.

7. Patients with adequate hepatic function (total bilirubin must be < 2.0 times the upper
limit of the institutional normal range; alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) must be < 3.0 times the upper limit of the institutional normal
range). Test results must be no more than 3 months old.

8. Patients willing and able to review, understand, and provide written consent.

Exclusion Criteria:

1. Patients continuously taking any minocycline within the last 15 days. Patients who
have conditions that potentially preclude use of minocycline as determined by the
treating physician.

2. Patients continuously taking systemic steroids within the last 15 days.

3. Patients with autoimmune disorders (for example, systemic lupus erythematosus or
rheumatoid arthritis), who have been treated in the last 3 years.

4. Patients who are pregnant; the absence of pregnancy will be confirmed by negative
urine test.

5. Hypersensitivity to any tetracyclines, or a history of other allergies or drug
reactions that in the treating physician's judgment make the patient inappropriate for
this study.

6. Patients receiving vitamin K antagonist (warfarin).

7. Patients with a BMI >40 (Obese Class III criteria).

8. Patients who will receive cetuximab or other targeted therapy where physicians may use
topical doxycycline to reduce the rash associated with therapy.