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

NCT03144804 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-044
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Cancer Metastatic

Keywords

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI, complete response (CR) is the disappearance of all target lesions and partial response (PR) is a \>/=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

  2 years

Secondary Outcomes (3)

• Progression Free Survival

  2 years

• Overall Survival

  up to 2 years

• Overall Disease Control Rate

  up to 2 years

Study Arms (1)

Lamivudine

EXPERIMENTAL

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

Drug: Lamivudine

Interventions

Lamivudine DRUG

This drug may help prevent the growth and spread of the cancer cells to other parts of the body.

Also known as: Combivir

Lamivudine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Lamivudine; lamivudine, zidovudine drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: Aparna Parikh, MD
• Organization: Massachusetts General Hospital

aparna.parikh@mgh.harvard.edu

617-339-8452

Study Officials

• Aparna R. Parikh, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 5, 2017
• First Posted: May 9, 2017
• Study Start: October 31, 2017
• Primary Completion: March 26, 2020
• Study Completion: September 27, 2022
• Last Updated: June 6, 2024
• Results First Posted: August 26, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)