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

NCT07435584 | Not Yet Recruiting Phase 1

• 1 other identifier: Everolimus-001
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; CDK12; Everolimus

Outcome Measures

Primary Outcomes (2)

• 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

  First 8 weeks after initial dose

• 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

  Assessed every 8 weeks up to 24 months

Secondary Outcomes (6)

• Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)

  Up to 8 weeks

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

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

• Progression-Free Survival (PFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Disease Control Rate (DCR)

  Assessed every 8 weeks up to 24 months

Study Arms (1)

Everolimus Treatment

EXPERIMENTAL

Participants 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.

Drug: Everolimus (Afinitor) tablets

Interventions

Everolimus (Afinitor) tablets DRUG

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.

Everolimus Treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Everolimus; Tablets

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)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Xiangxing Kong

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiangxing Kong

CONTACT

+8615068803769; kongxiangxing@zju.edu.cn

Jianqing YU

CONTACT

+8619521531205; jianqingyu@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: February 22, 2026
• First Posted: February 27, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The access method will be stated when the research results are published.
• Access Criteria: To access the Individual Participant Data (IPD), a detailed data usage plan must be submitted, specifying the research objectives and study content, which will be approved following review by the Principal Investigator (PI) of this study.