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Metastatic Colorectal CancerPhase 2NCT06543836

ctDNA-guided Treatment of TKI Plus PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer

A Phase 2 study testing Sintilimab, Fruquintinib or Regorafenib and Fruquintinib in people with Metastatic Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The efficacy of combining TKI with PD-1 inhibitor in the treatment of advanced MSS/pMMR colorectal cancer with low levels of maxVAF in peripheral blood ctDNA failed with standard treatment was assessed, compared to standard treatment as chosen by researchers. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Sintilimab, Fruquintinib or Regorafenib and Fruquintinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
1 siteChina
Study dates
1 Dec 2023to 30 Nov 2025
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Age range between 18 and 80 years old.
  • ECOG performance status of 0 or 1.
  • Histologically confirmed advanced or recurrent colorectal adenocarcinoma.
  • Confirmed normal expression of mismatch repair proteins (pMMR) by immunohistochemistry or microsatellite stable (MSS) by PCR/next-generation sequencing.
  • Blood ctDNA maxVAF <6.5% as detected by NGS. blood samples of 8-10ml are to be collected from a qualified testing company for analysis.
  • Metastatic colorectal cancer that has failed with previous treatment with fluoropyrimidine (5-fluorouracil or capecitabine), oxaliplatin, irinotecan plus bevacizumab/cetuximab (left-side RAS/BRAF wildtype).
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  • At least 28 days since the last systemic therapy (oral fluoropyrimidine ≥ 14 days), with the option of receiving palliative radiation therapy to limited areas if completed more than 3 weeks prior.
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1).
  • Expected survival of at least 3 months.
  • Adequate organ and bone marrow function, with laboratory values within the following limits within 7 days before enrollment:
  • Complete blood count: Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count (PLT) ≥100×10^9/L, Hemoglobin (HGB) ≥9.0 g/dL.
  • Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN, or ≤5× ULN in the presence of liver metastasis.
  • Kidney function: Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50ml/min, Urinalysis showing urine protein <2+, for patients with baseline urine protein ≥2+, 24-hour urine protein collection should show <1g.
  • Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 times ULN.
  • Normal electrocardiogram, left ventricular ejection fraction (LVEF) ≥50%.
  • No history of other malignancies, except for cured cervical carcinoma in situ, non-melanoma skin cancer, non-invasive bladder tumors, non-invasive lung cancer, or malignant tumors with continuous disease-free survival of ≥5 years following surgical resection.
  • Negative pregnancy test for women of childbearing potential, and willingness to use effective contraception during the clinical trial period.
  • Voluntary participation in the clinical trial with informed consent provided.

Who cannot join

  • Patients with a history of prior treatment with fruquintinib or similar small molecule oral targeted drugs primarily aimed at anti-angiogenesis (including marketed or investigational drugs).
  • Patients with a history of prior treatment with other PD-1/PD-L1/CTLA-4 antibody therapies or other immunotherapies targeting PD-1/PD-L1/CTLA-4.
  • Patients who experienced severe hypersensitivity reactions after monoclonal antibody administration in the past.
  • Patients with any active autoimmune disease or a history of autoimmune diseases (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, and patients requiring bronchodilators for medical intervention for asthma cannot be included). however, the following patients are allowed to be included: patients with vitiligo, psoriasis, alopecia that do not require systemic treatment, well-controlled type I diabetes, and hypothyroidism with normal thyroid function under replacement therapy.
  • Patients who require immunosuppressive agents, systemic corticosteroids, or absorbable local steroid therapy for achieving immunosuppression (dose >10mg/day prednisone or equivalent) and are still on continued therapy within 2 weeks of initial dosing.
  • Patients with various factors affecting oral drug intake (such as dysphagia, post-gastrointestinal surgery, chronic diarrhea, and intestinal obstruction).
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  • Patients with uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
  • Patients with any signs or history of bleeding diathesis regardless of severity, patients who experienced any bleeding event ≥CTCAE Grade 3 within 4 weeks before initial dosing, or patients with unhealed wounds, fractures, active peptic ulcers, ulcerative colitis, or other gastrointestinal diseases with active bleeding or other conditions deemed by the investigator to potentially cause severe gastrointestinal bleeding or perforation.
  • Patients with known brain metastases with a history of organ transplantation.
  • Patients who received approved or investigational anti-tumor treatments within 4 weeks before the start of the study, including but not limited to chemotherapy, surgery, radiotherapy (within 3 weeks), biologically targeted therapy, interventional therapy, immunotherapy, and traditional Chinese medicine treatment for cancer (as per the indications in the traditional Chinese medicine instructions, participants can be included after a 2-week washout period) (Note: oral fluoropyrimidine drugs for less than 14 days, patients with adverse events from previous treatments, excluding alopecia, not recovered to ≤CTCAE Grade 1).
  • Patients vaccinated with preventive or attenuated vaccines within 4 weeks before the first dose.
  • Patients with any severe and/or uncontrolled diseases, including:
  • patients with suboptimal blood pressure control (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥90 mmHg).
  • patients who had thrombotic events, cerebrovascular accidents, myocardial infarctions, ≥Grade 2 congestive heart failure, or requiring treatment for arrhythmias (including QTc ≥480ms) within 6 months before the first dose.
  • patients with active or uncontrolled severe infections (≥CTCAE Grade 2 infections), tuberculosis patients.
  • patients with a clinically significant history of liver disease, including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1 × 10^4 copies/mL or >2000 IU/mL), known hepatitis C virus infection (HCV) and HCV RNA positive (>1 × 10^3 copies/mL), or other decompensated liver diseases, chronic hepatitis requiring antiviral treatment.
  • HIV positive.
  • poorly controlled diabetes (fasting blood sugar ≥CTCAE Grade 2).

Trial locations and contacts

1 site in 1 country.

Aiping Zhou, M.D. contact

8610-13691161998

zhouap1825@126.com

China1 site, 1 recruiting
  • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

    Beijing, Beijing Municipality, 100021

    Aiping Zhou, M.D., 8610-13691161998, zhouap1825@126.com

    Aiping Zhou, M.D.

    Recruiting

Other trials in China

About this study

Official title: ctDNA-guided Treatment of an Anti-angiogenic TKI Combined With a PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer Failed With Standard Therapy: a Randomized Controlled Phase 2 Clinical Trial

The efficacy of combining TKI with PD-1 inhibitor in the treatment of advanced MSS/pMMR colorectal cancer with low levels of maxVAF in peripheral blood ctDNA failed with standard treatment was assessed, compared to standard treatment as chosen by researchers.

Read the detailed description

This study is a prospective, randomized phase II controlled trial. It will include patients with histologically confirmed advanced metastatic pMMR/MSS colorectal adenocarcinoma, who have failed with treatment with fluoropyrimidine (5-fluorouracil or capecitabine), oxaliplatin, irinotecan plus bevacizumab/cetuximab (left-side RAS/BRAF wild-type) and whose peripheral blood ctDNA test shows a maxVAF level lower than 6.5%. Patients will be randomly assigned to receive a TKI + a PD-1 inhibitor (primarily fruquintinib combined with sintilimab) or standard later-line treatment options (regorafenib or fruquintinib monotherapy, at the discretion of the investigator) until disease progression, death, intolerable adverse events, or withdrawal of informed consent.

Being tested
Sintilimab, Fruquintinib or Regorafenib, Fruquintinib
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • SintilimabDrug

    Also called PD-1 inhibitor

    Sintilimab 200mg, d1, with a treatment cycle of 21 days, and efficacy assessment every 2 cycles.

  • Fruquintinib or RegorafenibDrug

    Also called TKI

    The treatment regimen consists of the following options:

    Option 1: Fruquintinib 5mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months.

    Option 2: Regorafenib 160mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months.

  • FruquintinibDrug

    Also called TKI

    Fruquintinib 5mg Qd, d1-14, with a treatment cycle of 21 days, and efficacy assessment every 2 cycles.

Study groups in NCT06543836
Study groupRoleWhat they receive
PD-1 inhibitor+Tyrosine kinase inhibitor(TKI)ExperimentalPD-1 inhibitor: Sintilimab 200mg, d1, TKI: Fruquintinib 5mg Qd, d1-14, Q3w. Efficacy assessment every 2 cycles.
Receives: Drug: Sintilimab; Drug: Fruquintinib
Tyrosine kinase inhibitor(TKI)Active comparatorThe treatment regimen consists of the following options: Option 1: Fruquintinib 5mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months. Option 2: Regorafenib 160mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months.
Receives: Drug: Fruquintinib or Regorafenib

What is being measured

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

  1. PFS

    Progression-free survival

    Measured: Up to 2 years

Secondary outcomes (3)
  1. OS

    Overall survival

    Measured: Up to 2 years

  2. ORR

    Objective response rate

    Measured: Up to 2 years

  3. DCR

    Disease control rate

    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.

  1. First posted9 Aug 2024
  2. Study start1 Dec 2023
  3. Primary completion30 Nov 2025 (estimated)
  4. Study completion30 Nov 2025 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
68 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06543836
Sponsor's protocol ID
NCC4663
Status last verified
Aug 2024
First submitted
15 Jul 2024
Last updated
9 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sintilimab, Fruquintinib or Regorafenib and Fruquintinib in people with Metastatic Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site 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 18 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 9 Aug 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 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Aiping Zhou, M.D. (8610-13691161998, zhouap1825@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PFS (time frame: Up to 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 9 Aug 2024.

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