Colon CancerPhase 2NCT06301386
Everolimus Combined With PD-1 in Advanced Colorectal Cancer Patients
A Phase 2 study testing Everolimus and PD-1 in people with Colon Cancer, run by Fudan University at 2 sites in China.
Trial summary
The goal of this clinical trial is to learn about efficacy of Everolimus in combination with PD-1 in patients with locally advanced and advanced colorectal cancer that cannot be R0 resected. The main question is to explore the survival time, safety and tolerability of the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer
- What is being tested?
- Everolimus and PD-1
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesChina
- Study dates
- 1 Apr 2024to 1 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Age ≥18 years old, both sexes;
- Patients with histologically or cytologically confirmed locally advanced and advanced colorectal cancer that cannot be R0 resected;
- Recist1.1-defined disease progression or intolerance to prior standard therapy during or after standard therapy. Standard therapy was required to include all the following agents: fluorouracilines, chemotherapy agents such as irinotecan, and oxaliplatin, with or without an anti-VEGF monoclonal antibody (e.g., bevacizumab). Left-sided KRAS/NRAS/BRAF wild-type subjects received combined anti-EGFR mAb (cetuximab or panitumumab).
- Before enrollment, the tumor tissue was PTEN mutations;
- Patients with ECOG score of 0-1 and expected survival time ≥3 months, patients who can cooperate to observe adverse reactions and efficacy;
- At least one measurable tumor lesion according to RECIST 1.1 criteria;
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- Good organ function:
- neutrophil ≥1.5*109/L; Platelet ≥100*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl;
- Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and T4 in the normal range;
- bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the upper limit of normal;
- Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥60ml/min;
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the upper limit of the normal range, unless the patient is receiving anticoagulant therapy and the PT value is within the intended range for anticoagulant therapy;
- Activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of normal;
- There were no serious concomitant diseases that could make the survival time less than 5 years;
- Negative pregnancy test in female subjects (for female patients of childbearing potential); Infertile female patients;
- Male patients of childbearing potential and female patients of childbearing potential and at risk of pregnancy must agree to use adequate contraception for the entire duration of the study and for 12 months after receiving treatment with the protocol;
- Signed and dated informed consent indicating that the patient has been informed about all relevant aspects of the study;
- Patients who are willing and able to comply with the visit schedule, treatment plan, laboratory tests, and other study procedures;
- Willing to comply with the arrangement during the study period can not participate in any other clinical research on drugs and medical devices.
Who cannot join
- Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal tumor;
- Prior treatment with PD-1 antibody;
- Prior treatment with mTOR inhibitor;
- Previous or concurrent history of other malignant tumors, excluding adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
- Active autoimmune disease, history of autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); It does not include autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes on stable doses of insulin; Vitiligo or cured childhood asthma/allergy without any intervention in adulthood;
- A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
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- Contraindications to antiangiogenic drugs (such as active bleeding, gastrointestinal bleeding, hemoptysis, etc.);
- History of interstitial lung disease (excluding radiation pneumonitis without steroid treatment) and non-infectious pneumonia;
- Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
- The subject has active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay)
- Severe cardiopulmonary and renal dysfunction;
- Have hypertension that is not well controlled with antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
- A history of psychotropic substance abuse, alcohol or drug abuse;
- Other factors that may affect subject safety or trial compliance as judged by the investigator. Severe medical conditions requiring concomitant treatment (including mental illness), serious laboratory abnormalities, or other family or social factors.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
Anyang Tumor Hospital
Anyang, Henan
Yanjun Wang, PhD, +8613837266702, m13837266702@163.com
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality
Dawei Li, PhD, +8613774201693, li_dawei@fudan.edu.cn
About this study
Official title: The Combination of Everolimus and PD-1 in the Treatment of Locally Advanced and Advanced Colorectal Cancer That Cannot be R0 Resected
The goal of this clinical trial is to learn about efficacy of Everolimus in combination with PD-1 in patients with locally advanced and advanced colorectal cancer that cannot be R0 resected. The main question is to explore the survival time, safety and tolerability of the treatment. At the same time, the correlation between biomarkers (including PD-L1 expression, tumor mutation load, lymphocyte subpopulation, cytokines, TCR, intestinal microbes, and others) and the efficacy and drug resistance mechanism will be analyzed, so as to provide reference for the subsequent guidance of the screening of benefit groups.
Read the detailed description
Everolimus is an oral protein kinase inhibitor of the mTOR (mammalian target of rapamycin) serine/threonine kinase signal transduction pathway. Studies have shown that immunotherapy combined with protein kinase inhibitor has initial efficacy in the treatment of colorectal cancer. Therefore, the objective of this study is to evaluate the efficacy and safety of Everolimus in combination with PD-1 in patients with locally advanced and advanced colorectal cancer that cannot be R0 resected.
- Conditions
- Colon Cancer
- Being tested
- Everolimus, PD-1
- Keywords
- mTOR inhibitor, immunotherapy
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
PD-1Drug
200mg intravenously every 3 weeks (Q3W), was administered until the occurrence of unacceptable toxic effects, or disease progression, withdrawal of consent, or withdrawal as judged by the investigator.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus in combination with PD-1 | Experimental | Patients will be treated with Everolimus and PD-1 Receives: Drug: Everolimus; Drug: PD-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate (ORR)
The proportion of participants whose best outcome is complete remission or partial remission
Measured: 2 year
Secondary outcomes (4)
progression-free survival (PFS）
Time from initiation of treatment to disease progression or death from any cause.
Measured: 2 year
overall survival (OS)
The time between the start of the participants' treatment and their death from any cause.
Measured: 2 year
disease control rate (DCRs)
The proportion of patients without disease progression (PD).
Measured: 2 year
advert events
Assessment of the safety profile of regimen according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0).
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2024
- Study start1 Apr 2024 (estimated)
- Primary completion1 May 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Anyang Tumor Hospital
- Responsible party
- Principal investigator, Li Dawei, Fudan University
- Investigators
- Dawei Li, PhD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06301386
- Sponsor's protocol ID
- EVOLUTION
- Status last verified
- Mar 2024
- First submitted
- 3 Mar 2024
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Combination of Everolimus and PD-1 in the Treatment of Locally Advanced and Advanced Colorectal Cancer That Cannot be R0 Resected
- ClinicalTrials.gov ID
- NCT06301386
- Acronym / sponsor ID
- EVOLUTION
- Conditions
- Colon Cancer
- Keywords
- mTOR inhibitor, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Collaborators
- Anyang Tumor Hospital
- Study start
- 1 Apr 2024 (estimated)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 8 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn about efficacy of Everolimus in combination with PD-1 in patients with locally advanced and advanced colorectal cancer that cannot be R0 resected. The main question is to explore the survival time, safety and tolerability of the treatment. At the same time, the correlation between biomarkers (including PD-L1 expression, tumor mutation load, lymphocyte subpopulation, cytokines, TCR, intestinal microbes, and others) and the efficacy and drug resistance mechanism will be analyzed, so as to provide reference for the subsequent guidance of the screening of benefit groups.
Detailed description
Everolimus is an oral protein kinase inhibitor of the mTOR (mammalian target of rapamycin) serine/threonine kinase signal transduction pathway. Studies have shown that immunotherapy combined with protein kinase inhibitor has initial efficacy in the treatment of colorectal cancer. Therefore, the objective of this study is to evaluate the efficacy and safety of Everolimus in combination with PD-1 in patients with locally advanced and advanced colorectal cancer that cannot be R0 resected.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus in combination with PD-1 | Experimental | Drug: Everolimus, Drug: PD-1Patients will be treated with Everolimus and PD-1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age ≥18 years old, both sexes;
- Patients with histologically or cytologically confirmed locally advanced and advanced colorectal cancer that cannot be R0 resected;
- Recist1.1-defined disease progression or intolerance to prior standard therapy during or after standard therapy. Standard therapy was required to include all the following agents: fluorouracilines, chemotherapy agents such as irinotecan, and oxaliplatin, with or without an anti-VEGF monoclonal antibody (e.g., bevacizumab). Left-sided KRAS/NRAS/BRAF wild-type subjects received combined anti-EGFR mAb (cetuximab or panitumumab).
- Before enrollment, the tumor tissue was PTEN mutations;
- Patients with ECOG score of 0-1 and expected survival time ≥3 months, patients who can cooperate to observe adverse reactions and efficacy;
Key exclusion criteria (14 listed)
- Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal tumor;
- Prior treatment with PD-1 antibody;
- Prior treatment with mTOR inhibitor;
- Previous or concurrent history of other malignant tumors, excluding adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
- Active autoimmune disease, history of autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); It does not include autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes on stable doses of insulin; Vitiligo or cured childhood asthma/allergy without any intervention in adulthood;
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 |
|---|---|---|
| EverolimusPatients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. | Drug | Everolimus in combination with PD-1 |
| PD-1200mg intravenously every 3 weeks (Q3W), was administered until the occurrence of unacceptable toxic effects, or disease progression, withdrawal of consent, or withdrawal as judged by the investigator. | Drug | Everolimus in combination with PD-1 |
Primary outcome
objective response rate (ORR)
Time frame: 2 year
The proportion of participants whose best outcome is complete remission or partial remission
4 secondary outcomes
progression-free survival (PFS）
Time frame: 2 year
overall survival (OS)
Time frame: 2 year
disease control rate (DCRs)
Time frame: 2 year
advert events
Time frame: 2 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
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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.
Dawei Li, PhD principal investigator
Fudan University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and PD-1 in people with Colon Cancer, run by Fudan University at 2 sites in China.
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 19 inclusion and 14 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: opening soon, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dawei Li, PhD (+8613774201693, li_dawei@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response rate (ORR) (time frame: 2 year). 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 8 Mar 2024.