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Lamivudine in Treating Patients with p53 Mutant Stage IV Colorectal Cancer

Trial Status: Closed to Accrual

This phase II trial studies how well lamivudine works in treating patients with p53 mutant stage IV colorectal cancer. Lamivudine may impair the ability of p53 mutant tumor 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 Clinical Laboratory Improvement Act (CLIA) approved genetic test; only known loss of function TP53 mutation/deletion will be eligible for this study
  • Participants must have measurable 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 > 20 mm with conventional techniques or > 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI) or calipers by clinical exam
  • Patients must be resistant to or intolerant of fluorouracil (5FU), oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab (if RAS wild type)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 8 weeks
  • Absolute neutrophil count >= 1,200/mcL
  • Platelets >= 75,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal within normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR
  • Estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m^2 for participants with creatinine levels not within institutional normal OR
  • Creatinine clearance (calculated per Cockcroft-Gault equation) >= 60 mL/min for participants with creatinine levels not within 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 3 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 3 weeks earlier; radiotherapy maybe administered within 3 weeks of study entry at the discretion of the investigator and treating physician
  • 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
  • Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lamivudine
  • Hepatitis B virus (HBV) positive participants will be excluded given the known effects of lamivudine on HBV


Massachusetts General Hospital Cancer Center
Contact: Aparna Raj Parikh
Phone: 617-724-4000


I. To determine the response rate of lamivudine in patients with stage 4 colorectal cancer who are p53 mutated.


I. To determine the progression free survival.

II. To determine the overall survival.

III. To document changes in human satellite II (HSATII) expression in circulating tumor cells of patients on treatment.

IV. To document changes in HSATII expression in tumors of patients on lamivudine.


Patients receive lamivudine orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Aparna Raj Parikh

  • Primary ID 17-044
  • Secondary IDs NCI-2017-01688
  • ID NCT03144804