The goal of this clinical research study is to learn if minocycline can reduce numbness, pain, and/or loss of motor function in patients with colorectal cancer. In this study, minocycline will be compared to a placebo.

The study doctor can explain how the study drug is designed to work.

A placebo is not a drug. It looks like the study drug, but it is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

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.

The adverse events were monitoring/assessed from the first dose of study medication, up to 30 days after the last dose.