Clinical Trials /

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

NCT03144804

Description:

This research study is studying a drug as a possible treatment for p53 mutant metastatic colorectal cancer. The drug involved in this study is: -Lamivudine

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer
  • Official Title: A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-044
  • NCT ID: NCT03144804

Conditions

  • Colorectal Cancer Metastatic

Interventions

DrugSynonymsArms
LamivudineCombivirLamivudine

Purpose

This research study is studying a drug as a possible treatment for p53 mutant metastatic colorectal cancer. The drug involved in this study is: -Lamivudine

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
LamivudineExperimentalLamivudine administered orally every 4 weeks Treatment cycles will last 28 consecutive days The dosage will be determine by the PI
  • Lamivudine

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Disease Control Rate
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Colorectal Cancer

Last Updated

May 5, 2017