A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug to learn whether the drug works in treating a
specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved lamivudine for this specific
disease but it has been approved for other uses.

In this research study, the investigators are studying the effects of lamivudine on this type
of cancer. This drug may help prevent the growth and spread of the cancer cells to other
parts of the body. The investigators have discovered that this particular type of colon
cancer, which has a p53 mutation may be sensitive to treatment with lamivudine by impairing
the ability of the cancer cells to grow.

Inclusion Criteria:

- Patients must have histologically confirmed adenocarcinoma of the colon that has
metastasized (stage 4) and is TP53 mutant/deleted by a CLIA approved genetic test.
Only known loss of function TP53 mutation/deletion will be eligible for this study.

- Participants must have measureable disease, defined as at least on lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as > 20mm with conventional
techniques or > 10 mm with spiral CT scan, MRI or calipers by clinical exam. See
section 11 for evaluation of measurable disease

- Patients must be resistant to or intolerant of 5FU, oxaliplatin, irinotecan,
bevacizumab and cetuximab/panitumumab (if RAS wild type)

- Age 18 or older.

- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

- Life expectancy of greater than 8 weeks.

- Participants must have normal organ and marrow function as defined below:

- absolute neutrophil count ≥1,200/mcL

- platelets ≥75,000/mcL

- total bilirubin ≤1.5 × institutional upper limit of normal within normal

- AST(SGOT)/ALT(SGPT) ≤5 × institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

- The effects of lamivudine on the developing human fetus are known to be teratogenic.
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 she or her partner is participating in this study, she
should inform her treating physician immediately. Men treated or enrolled on this
protocol must also agree to use adequate contraception prior to the study, for the
duration of study participation, and 4 months after completion of lamivudine
administration.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosourea or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Participants who are receiving any other investigational agents.

- Participants with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lamivudine.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because lamivudine is an agent 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 lamivudine, breastfeeding should be discontinued if the mother is treated
with lamivudine.

- HIV-positive participants on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with lamivudine

- HBV positive participants will be excluded given the known effects of lamivudine on
HBV.