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Colorectal CancerPhase 1/2EVER-RECODENCT07435584

Everolimus in CDK12-Deficient Metastatic Colorectal Cancer (EVER-RECODE)

A Phase 1/2 study testing Everolimus (Afinitor) tablets in people with Colorectal Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a prospective, open-label, multicenter, single-arm Phase Ib/II study evaluating the safety and preliminary efficacy of everolimus in patients with CDK12-deficient refractory metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Colorectal Cancer
What is being tested?
Everolimus (Afinitor) tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
No sites listed yet
Study dates
1 Mar 2026to 31 Dec 2028
Phase
Phase 1/2
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and voluntarily sign an ethics committee-approved informed consent form and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Age 18 to 80 years (inclusive) at the time of signing informed consent; male or female.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Estimated life expectancy ≥12 weeks.
  • CDK12 deficiency confirmed by immunohistochemistry (IHC).
  • Histologically confirmed metastatic colorectal cancer with documented disease progression after prior standard systemic antitumor therapies, including but not limited to oxaliplatin, fluoropyrimidine, and irinotecan.
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  • o Patients with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) tumors must have experienced disease progression following anti-PD-1/PD-L1 therapy.
  • At least one measurable lesion according to RECIST version 1.1, defined as:
  • Non-nodal lesions ≥10 mm in longest diameter by CT scan (slice thickness ≤5 mm);
  • Malignant lymph nodes with short axis ≥15 mm by CT scan (slice thickness ≤5 mm recommended).
  • Adequate organ function meeting all of the following criteria:
  • Hematologic (without growth factor support or transfusion within 7 days prior to testing):
  • Absolute neutrophil count ≥1.5 × 10⁹/L
  • Platelet count ≥75 × 10⁹/L
  • Hemoglobin ≥90 g/L
  • Biochemical:
  • Total bilirubin ≤1.5 × upper limit of normal (ULN)
  • AST and ALT ≤2.5 × ULN
  • Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min (calculated using Cockcroft-Gault formula)
  • Coagulation:
  • International normalized ratio (INR) ≤1.5
  • Activated partial thromboplastin time (aPTT or PTT) ≤1.5 × ULN
  • Absence of high-risk conditions, including:
  • Active or major cardiovascular events within 6 months (e.g., myocardial infarction, severe heart failure, stroke);
  • Severe pulmonary dysfunction requiring long-term oxygen therapy or interstitial lung disease/pulmonary fibrosis;
  • Active uncontrolled infection (including uncontrolled HBV, HCV, HIV, or tuberculosis);
  • Other active malignancies within 5 years, except those treated with curative local therapy.
  • For participants of childbearing potential:
  • Must agree to use effective contraception during the study and for 120 days after completion;
  • Negative serum pregnancy test within 7 days prior to enrollment;
  • Not breastfeeding.

Who cannot join

  • Participants meeting any of the following criteria will be excluded:
  • Untreated or active central nervous system (CNS) metastases. Patients with a history of leptomeningeal metastases or current leptomeningeal disease.
  • Receipt of systemic antitumor therapy within 4 weeks prior to initiation of study treatment.
  • For prior small-molecule targeted therapy: the interval between the end of prior therapy and first study dose must be ≥5 half-lives of the drug or ≥7 days, whichever is longer.
  • For prior traditional Chinese antitumor medicines: ≥2 weeks washout is required.
  • Palliative radiotherapy to non-target lesions, radioactive seed implantation, radiofrequency ablation, or similar local therapy within 28 days prior to first study dose.
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  • Toxicities or complications from prior therapies that have not recovered to NCI-CTCAE grade ≤1 or to eligibility-specified levels.
  • o Patients with stable grade ≤2 toxicities may be enrolled at investigator discretion if no safety risk exists (e.g., immune checkpoint inhibitor-related type 1 diabetes or hypothyroidism controlled with hormone replacement therapy).
  • Within 28 days prior to first study dose: inability to swallow oral medication, chronic diarrhea, active gastroenteritis, gastrointestinal perforation, prior major gastrointestinal resection, colitis, or other conditions that may impair drug administration or absorption.
  • Clinically symptomatic moderate or severe ascites requiring therapeutic paracentesis or drainage within 2 weeks prior to study treatment.
  • Small asymptomatic ascites detected by imaging is allowed.
  • Uncontrolled or moderate-to-large pleural effusion or pericardial effusion.
  • Evidence of intestinal obstruction or signs/symptoms of obstruction at baseline.
  • Patients who underwent surgery with complete resolution of obstruction may be screened.
  • Presence of an indwelling intestinal stent at screening.
  • Uncontrolled or severe cardiovascular disease, including:
  • Severe or unstable congestive heart failure (NYHA class II-IV)
  • Myocardial infarction within 6 months prior to first dose
  • Unstable angina within 1 month prior to treatment
  • Unstable arrhythmia
  • History of or concurrent malignancies other than colorectal cancer, unless in complete remission for ≥5 years prior to screening and not requiring ongoing therapy, except:
  • Basal cell carcinoma of the skin
  • Superficial bladder cancer
  • Cutaneous squamous cell carcinoma
  • Cervical carcinoma in situ
  • Localized prostate cancer
  • Ductal carcinoma in situ after curative surgery
  • Non-metastatic prostate or breast cancer receiving hormone therapy
  • Severe infection within 28 days prior to first dose, including infections requiring hospitalization, bacteremia, or severe pneumonia.
  • Active infection requiring therapeutic intravenous antibiotics within 2 weeks prior to treatment.
  • Prophylactic antibiotics (e.g., for urinary tract infection prevention) are permitted.
  • Active hepatitis B infection defined as:
  • o Positive HBsAg AND HBV DNA ≥10,000 copies/mL (≥2,000 IU/mL).
  • Active hepatitis C defined as:
  • o Positive HCV antibody AND detectable HCV RNA.
  • Active pulmonary tuberculosis within 1 year prior to enrollment, or history of active tuberculosis >1 year prior without appropriate standard treatment.
  • Known immunodeficiency, including HIV positivity, congenital or acquired immunodeficiency disorders, or history of organ transplantation.
  • Active autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, myasthenia gravis, or requirement for long-term systemic immunosuppressive therapy.
  • Concomitant use of strong CYP3A4 inhibitors or inducers that cannot be discontinued ≥7 days prior to first dose (e.g., ketoconazole, itraconazole, clarithromycin, rifampin, carbamazepine, phenobarbital).
  • Active severe oral mucosal disease or recurrent oral ulceration.
  • o History of ≥grade 2 stomatitis that has not recovered to CTCAE grade ≤1.
  • Active dermatologic disorders (e.g., psoriasis, severe eczema, chronic pruritus) or prior ≥grade 2 drug-related skin reactions not fully resolved.
  • Prior treatment with everolimus and:
  • Development of ≥grade 3 drug-related toxicity, OR
  • Discontinuation due to resistance or lack of efficacy.
  • Known hypersensitivity to everolimus or any of its metabolites.
  • Pregnant or breastfeeding women, or women planning pregnancy during the study period.
  • Uncontrolled psychiatric illness, known alcohol or drug abuse, incarceration, or other conditions that may interfere with study compliance.
  • Any other condition that, in the investigator's judgment, may increase study risk, interfere with study outcomes, or make the participant unsuitable.
  • Inability to understand study conditions and objectives or refusal to sign informed consent.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Xiangxing Kong contact

+8615068803769

kongxiangxing@zju.edu.cn

Jianqing YU contact

+8619521531205

jianqingyu@zju.edu.cn

About this study

Official title: Everolimus in Refractory Metastatic Colorectal Cancer With CDK12 Deficiency: A Prospective Multicenter Phase Ib/II Study (EVER-RECODE)

This is a prospective, open-label, multicenter, single-arm Phase Ib/II study evaluating the safety and preliminary efficacy of everolimus in patients with CDK12-deficient refractory metastatic colorectal cancer.

Read the detailed description

Metastatic colorectal cancer (mCRC) remains a major cause of cancer-related mortality. Patients with refractory disease who have progressed after standard systemic therapies have limited treatment options and poor clinical outcomes. Identification of molecularly defined subgroups that may benefit from targeted therapeutic strategies represents an important unmet clinical need.

Cyclin-dependent kinase 12 (CDK12) plays a role in transcriptional regulation of genes involved in DNA damage response and genomic stability. CDK12 deficiency has been reported in a small subset of colorectal cancers, estimated at approximately 3-5% of cases. This molecular alteration may confer distinct biological characteristics and potential therapeutic vulnerabilities. However, the clinical efficacy of mTOR inhibition in CDK12-deficient metastatic colorectal cancer has not been prospectively evaluated.

EVER-RECODE adopts a combined Phase Ib/II study design. Phase Ib Component Design: Prospective, multicenter, open-label, single-arm study utilizing a traditional 3+3 dose-escalation design.

Objectives:

  • Evaluate the safety and tolerability of everolimus in patients with CDK12-deficient refractory mCRC.
  • Determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D).

Planned dose levels include 5 mg/day, 7.5 mg/day, and 10 mg/day administered orally once daily in continuous dosing. Although 10 mg/day has been widely used in several solid tumors, everolimus is associated with dose-dependent toxicities, particularly mucosal and dermatologic adverse events that frequently occur during early treatment. To ensure patient safety in this refractory population, the study adopts 5 mg/day as the starting dose, with stepwise escalation under close safety monitoring to identify the optimal tolerated dose.

Phase II Component Design: Prospective, multicenter, open-label, single-arm expansion study.

Objective:

  • Evaluate the preliminary antitumor activity of everolimus at the RP2D in patients with CDK12-deficient refractory mCRC.

Study Procedures Eligible participants must have metastatic colorectal cancer with CDK12 deficiency confirmed by immunohistochemistry (IHC). Participants will receive continuous daily oral everolimus. Radiologic tumor assessments will be performed every 8 weeks. Participants will be followed for safety and survival for up to 24 months.

Primary Endpoints Phase Ib: Incidence of dose-limiting toxicities (DLTs) and determination of MTD/RP2D.

Phase II: Objective response rate (ORR) assessed according to RECIST version 1.1.

Being tested
Everolimus (Afinitor) tablets
Keywords
Colorectal cancer, CDK12, Everolimus
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Everolimus (Afinitor) tabletsDrug

    Everolimus administered orally once daily in continuous treatment. Phase Ib dose levels include 5 mg/day, 7.5 mg/day, and 10 mg/day using a standard 3+3 dose-escalation design. Phase II participants will receive everolimus at the RP2D determined in Phase Ib.

Study groups in NCT07435584
Study groupRoleWhat they receive
Everolimus TreatmentExperimentalParticipants with CDK12-deficient refractory metastatic colorectal cancer will receive oral everolimus once daily. Phase Ib will follow a traditional 3+3 dose-escalation design (5 mg, 7.5 mg, 10 mg, oral, daily) for 8 weeks to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Phase II will evaluate efficacy at the RP2D.
Receives: Drug: Everolimus (Afinitor) tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose-Limiting Toxicities (DLTs)

    Dose-limiting toxicity (DLT) is defined as treatment-related toxicity occurring within the first 8 weeks (DLT observation window) that is assessed as definitely, probably, or possibly related to everolimus and meets any of the following criteria based on NCI-CTCAE version 5.0:

    • Grade ≥3 non-hematologic toxicity (excluding Grade 3 nausea/vomiting resolving within 48 hours with supportive care, Grade 3 alopecia, and Grade 3 fatigue without ECOG deterioration);
    • Grade 4 hematologic toxicity (including neutropenia lasting ≥7 days, thrombocytopenia with active bleeding, or hemoglobin <60 g/L requiring urgent transfusion);
    • Grade 3 hematologic toxicity persisting ≥14 days without recovery to ≤Grade 2;
    • Treatment interruption ≥14 days due to drug-related toxicity;
    • Other toxicities considered by the investigator to significantly compromise patient safety.

    For Phase Ib study

    Measured: First 8 weeks after initial dose

  2. Objective Response Rate (ORR)

    Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST version 1.1.

    For Phase II study

    Measured: Assessed every 8 weeks up to 24 months

Secondary outcomes (6)

  1. Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)

    Determination of the highest dose level at which ≤1 of 6 participants experiences DLT during the first 8 weeks (3+3 design).

    For Phase Ib study

    Measured: Up to 8 weeks

  2. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Incidence and severity of adverse events graded according to NCI-CTCAE version 5.0.

    For Phase Ib and Phase II study

    Measured: From first dose until end of treatment (up to 24 months)

  3. Progression-Free Survival (PFS)

    Time from first dose to disease progression per RECIST version 1.1 or death from any cause.

    For Phase II study

    Measured: Up to 24 months

  4. Overall Survival (OS)

    Time from first dose to death from any cause.

    For Phase II study

    Measured: Up to 24 months

  5. Disease Control Rate (DCR)

    Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST version 1.1.

    Measured: Assessed every 8 weeks up to 24 months

  6. Duration of Response (DoR)

    Time from first documented response (CR or PR) to disease progression or death.

    For Phase II study

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2026
  2. Study start1 Mar 2026 (estimated)
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07435584
Sponsor's protocol ID
Everolimus-001
Acronym
EVER-RECODE
Status last verified
Feb 2026
First submitted
22 Feb 2026
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: In accordance with the requirements of the International Committee of Medical Journal Editors, the de-identified raw data of this study will be made public after the results are published. The access method will be stated when the research results are published.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Everolimus (Afinitor) tablets in people with Colorectal Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.

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 31 inclusion and 50 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 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Xiangxing Kong (+8615068803769, kongxiangxing@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose-Limiting Toxicities (DLTs) (time frame: First 8 weeks after initial dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07435584.

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 27 Feb 2026.

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