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Colorectal CancerPhase 2REGOTORICOXNCT05933980

Toripalimab,Celecoxib and Regorafenib in the Treatment of Refractory Advanced Colorectal Cancer

A Phase 2 study testing Rego+Tori+Cele in people with Colorectal Cancer and Liver Metastases, run by Sun Yat-sen University 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 The sponsor has not verified this record for over two years, so it may be out of date.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

Research has found that patients with microsatellite instability (dMMR/MSI-H) type colorectal cancer can achieve long-term survival through immune checkpoint inhibitors (ICIs) treatment, but currently accounting for about 95% of MSS type mCRC, the benefits from immune checkpoint inhibitors are very limited. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Colorectal Cancer, Liver Metastases, MSS
What is being tested?
Rego+Tori+Cele
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteChina
Study dates
19 Dec 2023to 20 Dec 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 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • With subject's consent and signed informed consent form, willing and capable of following planned visits, research treatments, laboratory tests, and other trial procedures
  • Subjects diagnosed with colon or rectal adenocarcinoma by pathology or cytology have evidence of locally advanced lesions or metastases that cannot be surgically removed, without liver metastasis, and all other histological types are excluded.
  • Age 18 and above.
  • The subject has received at least second-line standard chemotherapy in the past and has failed. These standard treatment protocols must include fluorouracil, Oxaliplatin, irinotecan, and Bevacizumab. Subjects with left colon cancer RAS/BRAF V600E genotype of wild type must have received Cetuximab or Panitumumab and other Epidermal growth factor receptor inhibitors. The definition of treatment failure is: disease progression or intolerable toxic side effects occur during the treatment process or within 3 months after the last treatment (One or more chemotherapy drugs with a duration of ≥ 1 cycle for each frontline treatment until the disease progresses; adjuvant/neoadjuvant treatment is allowed in the early stage. If there is recurrence or metastasis during the adjuvant/neoadjuvant treatment or within 6 months after completion, adjuvant/neoadjuvant treatment is considered a failure of frontline systemic chemotherapy for advanced diseases.
  • The Eastern Cancer Cooperative Group's Physical Fitness Score (ECOG) is 0-1 points.
  • Clearly identify measurable lesions that meet the requirements of the evaluation criteria for solid tumor efficacy (RECIST version 1.1)
  • Based on the following laboratory test values obtained during the screening period, appropriate organ function is achieved: white blood cell count ≥ 3.3 × 109/L, neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 75 × 109/L, serum total bilirubin ≤ 1.5 × Upper limit of normal value (UNL), Aspartate transaminase or alanine aminotransferase ≤ 2.5 × UNL (liver metastasis subjects should be ≤ 5 × ULN), serum creatinine ≤ 1.5 × UNL.
  • Female subjects of childbearing age must carry out a serum Pregnancy test within 3 days before starting the study medication, and the result is negative, and are willing to use a medically approved effective contraceptive measure (such as Intrauterine device, contraceptives or condoms) during the study period and within 3 months after the last administration of the study medication.For male subjects whose partners are women of childbearing age, they should undergo surgical sterilization or agree to use effective methods of contraception during the study period and within 3 months after the last study administration.

Who cannot join

  • Previous or concurrent existence of other active malignant tumors (except malignant tumors that have received cured therapy and have not developed for more than 5 years or Carcinoma in situ that can be cured through adequate treatment);
  • At present, there are duodenal ulcer, Ulcerative colitis, Bowel obstruction and other digestive tract diseases or other conditions that may cause gastrointestinal bleeding or perforation as determined by researchers.
  • Thrombosis or embolism events occurred within 6 months before the study, such as cerebrovascular accident (including transient ischemic attack), Pulmonary embolism, Deep vein thrombosis.
  • Within the 6 months prior to enrollment in the study, the following conditions occurred: myocardial infarction, severe/unstable angina, NYHA grade 2 or above cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure.
  • Systemic use of antibiotics for ≥ 7 days within 4 weeks prior to enrollment in the study, or unexplained fever >38.5°C occurring during the screening period/before the first administration (according to the investigator's judgment, fever caused by tumor can be enrolled).
  • Major operations such as laparotomy, thoracotomy, organ removal through Laparoscopy or severe trauma were performed within 4 weeks before the study (Surgical incision should be completely healed before randomization);
Show all 18Show fewer
  • Within 7 days prior to enrollment in the study, there were uncontrollable pleural effusion, ascites, or pericardial effusion after effective treatment.
  • Immunosuppressive drugs were used within 7 days before the enrollment study, excluding nasal and inhaled Corticosteroid or systemic Sex hormone hormones with physiological dose (i.e. no more than 10mg /d prednisone or other Corticosteroid with physiological dose of equivalent drugs).
  • The general term standard for adverse events (NCICTCAE Version 5.0) caused by any previous treatment that has not yet subsided has toxicity of grade 2 or above (except anemia, hair loss, skin pigmentation and peripheral neurotoxicity related to Oxaliplatin).
  • There are any active, known or suspected autoimmune diseases. Subjects who were in a stable state at the time of enrollment and did not need systemic immunosuppression treatment, such as type I diabetes, hypothyroidism only requiring hormone replacement treatment, and skin diseases that did not need systemic treatment (such as Vitiligo, psoriasis, and alopecia) are allowed.
  • There are Interstitial lung disease, non infectious pneumonia or uncontrollable systemic diseases (such as diabetes, hypertension, Pulmonary fibrosis and acute pneumonia).
  • HIV (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; hepatitis C, defined as HCV-RNA higher than the detection limit of the analytical method) or co infection of hepatitis B and C.
  • Previously received antibodies against Programmed cell death protein-1 (PD-1) or its ligand (PD-L1), antibodies against cytotoxic T-lymphocyte associated protein 4 (CTLA-4), or other drugs/antibodies that act on the costimulation or checkpoint pathway of T cells.
  • Previous treatment with regofinib.
  • Medical history of known or suspected allergy to any relevant Drug allergy used in the study.
  • Pregnant or lactating women.
  • Women of childbearing age who have not used or refused to use effective non hormonal contraceptive methods (<2 years after their last menstrual period) or men who are at risk of giving birth.
  • The presence of other serious physical or mental illnesses or laboratory examination abnormalities may increase the risk of participating in the study, or interfere with the results of the study, as well as subjects deemed unsuitable by the researcher for participation in this study。

Trial locations and contacts

1 site in 1 country.

China1 site, 1 recruiting
  • Gastrointestinal Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510655

    Yanghong Deng, PhD, 008613925106525, dengyanh@mail.sysu.edu.cn

    Yanhong Deng, PhD

    Recruiting

Other trials in China

About this study

Official title: Combination of Regorafenib,Toripalimab and Celecoxib in Mismatch Repair (MMR) Proficient Refractory Advanced Colorectal Cancer Without Liver Metastasis:a Single Arm Phase II REGOTORICOX Study.

Research has found that patients with microsatellite instability (dMMR/MSI-H) type colorectal cancer can achieve long-term survival through immune checkpoint inhibitors (ICIs) treatment, but currently accounting for about 95% of MSS type mCRC, the benefits from immune checkpoint inhibitors are very limited. REGONIVO is a Phase Ib study to explore the efficacy and safety of regorafenib in combination with nivolumab in the treatment of gastric cancer and colorectal cancer with MSS. The study enrolled 50 patients with advanced disease, including 25 cases of gastric cancer, 25 cases of colorectal cancer, except for one case of colorectal cancer with MSI-H, and others were MSS type. The results of the study showed that patients with colorectal cancer had an objective response rate (ORR) of 36%.The ORR of liver matestasis vs. lung matestasis is 8.7% vs. 50%.

In this study, pMMR /MSS type patients with refractory advanced colorectal cancer without liver metastasis were selected as the subjects. Regorafenib, Toripalimab and Celecoxib were used to evaluate the maximum tolerable dose, objective response rate (ORR), total survival time (OS), progression free survival time (PFS), disease control rate (DCR), response duration (DoR) and safety of the subjects.

Read the detailed description

At present, the microsatellite stabilized (MSS) type of advanced refractory metastatic colorectal cancer (mCRC) has a poor median overall survival time of only about 7 months, and there is a significant unmet clinical demand for the efficacy of posterior treatment. Research has found that patients with microsatellite instability (dMMR/MSI-H) type colorectal cancer can achieve long-term survival through immune checkpoint inhibitors (ICIs) treatment, but currently accounting for about 95% of MSS type mCRC, the benefits from immune checkpoint inhibitors are very limited. REGONIVO is a Phase Ib study to explore the efficacy and safety of regorafenib in combination with nivolumab in the treatment of gastric cancer and colorectal cancer with MSS. The study enrolled 50 patients with advanced disease, including 25 cases of gastric cancer, 25 cases of colorectal cancer, except for one case of colorectal cancer with MSI-H, and others were MSS type. The results of the study showed that patients with colorectal cancer had an objective response rate (ORR) of 36%.The ORR of liver matestasis vs. lung matestasis is 8.7% vs. 50%.A phase Ib /Ⅱ clinical study REGOTORI enrolled 39 subjects, with a total ORR of 15.2%, and the ORR of non-liver metastasis subjects compared with liver metastasis subjects was 30% and 8.7% respectively. Based on the prospective small sample clinical trial results of other regifenib combined with PD-1 monoclonal antibody drugs, the overall ORR is between 0% and 33.3%, the ORR for non-liver metastases is between 20% and 50%, and the ORR for liver metastases is between 0% and 15%.

In this study, pMMR /MSS type patients with refractory advanced colorectal cancer without liver metastasis were selected as the subjects. Regorafenib, Toripalimab and Celecoxib were used to evaluate the maximum tolerable dose, objective response rate (ORR), total survival time (OS), progression free survival time (PFS), disease control rate (DCR), response duration (DoR) and safety of the subjects.

Being tested
Rego+Tori+Cele
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Rego+Tori+CeleDrug

    Also called Bayer AG, Innovent Biologics

    combination of Toripalimab,regorafenib and celecoxib

Study groups in NCT05933980
Study groupRoleWhat they receive
regorafenib,Toripalima and celecoxibExperimentalRegorafenib:in dose ramping stage,the initial dose is 80mg per dose, taken orally once a day. After 3 weeks of treatment, the medication is stopped for 1 week (i.e. from day 1 to day 21 and not from day 22 to day 28), with a treatment cycle of 4 weeks.The optimal recommended dose of regofinib (80mg, 120mg, or 160mg) obtained from the phase Ib dose ramping was included in the phase II study dose extension queue. Toripalimab:240mg, intravenous drip, administered every three weeks. celecoxib:200mg each time, taken orally twice a day.
Receives: Drug: Rego+Tori+Cele

What is being measured

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

  1. ORR

    objective response rate

    Measured: 1 years

Secondary outcomes (4)
  1. OS

    total survival time

    Measured: 2 years

  2. PFS

    progression free survival time

    Measured: 2 years

  3. DCR

    disease control rate

    Measured: 2 years

  4. DoR

    response duration

    Measured: 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 posted6 Jul 2023
  2. Study start19 Dec 2023
  3. Primary completion20 Sep 2025 (estimated)
  4. Study completion20 Dec 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05933980
Sponsor's protocol ID
GIHSYSU26
Acronym
REGOTORICOX
Status last verified
Feb 2024
First submitted
24 Jun 2023
Last updated
6 Feb 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.

    PubMed 28596308
  • Akin Telli T, Bregni G, Vanhooren M, Saude Conde R, Hendlisz A, Sclafani F. Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer. Cancer Treat Rev. 2022 Nov;110:102460. doi: 10.1016/j.ctrv.2022.102460. Epub 2022 Aug 27.

    PubMed 36058142
  • Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699.

    PubMed 33264544
  • Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Kuwata T, Togashi Y, Nishikawa H, Shitara K. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol. 2020 Jun 20;38(18):2053-2061. doi: 10.1200/JCO.19.03296. Epub 2020 Apr 28.

    PubMed 32343640
  • Wang F, He MM, Yao YC, Zhao X, Wang ZQ, Jin Y, Luo HY, Li JB, Wang FH, Qiu MZ, Lv ZD, Wang DS, Li YH, Zhang DS, Xu RH. Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis. Cell Rep Med. 2021 Aug 27;2(9):100383. doi: 10.1016/j.xcrm.2021.100383. eCollection 2021 Sep 21.

    PubMed 34622226

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rego+Tori+Cele in people with Colorectal Cancer and Liver Metastases, run by Sun Yat-sen University 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 8 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 6 Feb 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 Yanhong Deng, docter (020-38254084 ext. 86, dengyanh@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR (time frame: 1 years). 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 NCT05933980, which also lists 5 linked publications.

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 Feb 2024.

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