Colorectal Cancer MetastaticPhase 2NCT03144804
A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer
A Phase 2 study testing Lamivudine in people with Colorectal Cancer Metastatic, run by Massachusetts General Hospital at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2017to 27 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts general Hospital
Boston, Massachusetts, 02114
About this study
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
Read the 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.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- Lamivudine
- Keywords
- Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamivudineDrug
Also called Combivir
This drug may help prevent the growth and spread of the cancer cells to other parts of the body.
| Study group | Role | What they receive |
|---|---|---|
| Lamivudine | Experimental | * Lamivudine administered orally every 4 weeks
* Treatment cycles will last 28 consecutive days
* The dosage will be determine by the PI Receives: Drug: Lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (3)
Progression Free Survival
Progression-Free Survival (PFS) is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measured: 2 years
Overall Survival
Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive.
Measured: up to 2 years
Overall Disease Control Rate
Disease control rate (DCR) describes the percentage of patients with advanced cancer whose therapeutic intervention has led to a complete response (CR), partial response (PR), or stable disease (SD) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria:
- CR is the disappearance of all target lesions
- PR is at least a 30% decrease in the sum of the longest diameters of target lesions
- SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD)
- PD is at least a 20% increase in the sum of the longest diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progressions.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2017
- Study start31 Oct 2017
- Primary completion26 Mar 2020
- Study completion27 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aparna Parikh, Massachusetts General Hospital
- Investigators
- Aparna R. Parikh, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03144804
- Sponsor's protocol ID
- 17-044
- Status last verified
- May 2024
- First submitted
- 5 May 2017
- Last updated
- 6 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03144804
- Acronym / sponsor ID
- 17-044
- Conditions
- Colorectal Cancer Metastatic
- Keywords
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 26 Mar 2020 (actual)
- Study completion
- 27 Sep 2022 (actual)
- First posted
- 9 May 2017 (actual)
- Results
- Posted 26 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lamivudine | Experimental | Drug: Lamivudine* Lamivudine administered orally every 4 weeks * Treatment cycles will last 28 consecutive days * The dosage will be determine by the PI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LamivudineAlso: CombivirThis drug may help prevent the growth and spread of the cancer cells to other parts of the body. | Drug | Lamivudine |
Primary outcome
Overall Response Rate
Time frame: 2 years
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.
3 secondary outcomes
Progression Free Survival
Time frame: 2 years
Overall Survival
Time frame: up to 2 years
Overall Disease Control Rate
Time frame: up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aparna R. Parikh, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lamivudine in people with Colorectal Cancer Metastatic, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024.