Tyrosine Kinase Inhibitor (TKI) + Anti-PD-1 Antibody in TKI-responded Microsatellite Stability/Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Adenocarcinoma.

NCT04483219 | Unknown Phase 2

• 1 other identifier: TRAP
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of fruquintinib or regorafenib in combination with anti-PD-1 antibody in TKI (fruquintinib or regorafenib)-responded MSS/pMMR metastatic colorectal adenocarcinoma.

Conditions

MSS; pMMR; Metastatic Colorectal Adenocarcinoma

Keywords

tyrosine kinase inhibitors (TKIs); programmed cell death protein 1 (PD-1); microsatellite stable/proficient mismatch repair (MSS/pMMR); metastatic colorectal adenocarcinoma (mCRC); trial

Outcome Measures

Primary Outcomes (1)

• 9-month progression-free survival (PFS) rate (in subjects receiving TKI followed by TKI in combination with anti-PD-1 antibody)

  From the date of first dose of treatment to the first of either disease progression, relapse or death from any cause, evaluate patient PFS rate at 9 months

  9 months

Secondary Outcomes (8)

• Objective response rate (ORR)

  2 years

• Duration of response (DOR)

  2 years

• Disease control rate (DCR)

  2 years

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

Study Arms (1)

TKI ± anti-PD-1 antibody

EXPERIMENTAL

According to response to TKI, the combination of anti-PD-1 treatment would be determined.

Drug: TKI ± anti-PD-1 antibody

Interventions

TKI ± anti-PD-1 antibody DRUG

After one cycle of TKI, evaluations would be performed according to RECIST v 1.1. (1) obvious response (A): CR, PR or shrunken SD, or cavitation in metastatic lung lesions, or decrease in the density of liver metastatic targets ≥15%; (2) general response (B): enlarged SD; (3) poor response (C): PD. TKI ＋ anti-PD-1 antibody will be administered in group A. The subjects in group C will exit the study. The subjects in group B will continue TKI for another one cycle, the obvious response subjects will entered group A, the general response subjects will keep in arm B and continue the TKI monotherapy, and the poor response subjects will exit the study. 1. Fruquintinib 5mg or regorafenib 120mg, qd po, 3 weeks, Q4w. (The investigators decide to choose fruquintinib or regorafenib) 2. Toripalimab injection 240mg, Q3w, until the disease progresses or lasts for two years.

TKI ± anti-PD-1 antibody

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who voluntarily participated in the study, signed the written informed consent form, and could comply with the protocol of study.
• Male or female of age 18-75 years.
• Subjects with colorectal adenocarcinoma who were histopathologically confirmed, and with locally advanced (unresectable) or mCRC.
• Subjects who underwent standard antitumor therapies (fluorouracil, oxaliplatin, irinotecan were used, with or without administration of bevacizumab and/or cetuximab).
• Patients with MSS/pMMR mCRC (immunohistochemistry, polymerase chain reaction or next-generation sequencing can be used).
• All adverse reactions associated with drug use or surgery were reduced to grade 0-1 (according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) or to a level required by the protocol criteria.
• The presence of at least one measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI).
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
• Subjects with life expectancy ≥ 12 weeks.
• Adequate important organs functions: bone marrow function (neutrophil count ≥ 1.5×10\^9/L; platelet ≥ 80×10\^9/L; hemoglobin ≥ 90 g/L), liver function (serum albumin ≥ 28 g/L; total bilirubin ≤ 1.5×upper limit of normal (ULN); alanine aminotransferase and aspartate aminotransferase ≤ 3×ULN, or ≤ 5×ULN if liver metastases are present), renal function (serum creatinine ≤ 1.5×ULN or creatinine clearance (CrCl) ≥ 40 mL/min, using the Cockcroft-Gault formula; urine protein \< 2+; 24h urinary protein content \< 1.0 g/24h if urinary protein ≥ 2+ ), coagulation function (international normalized ratio or activated partial thromboplastin time ≤ 2×ULN), thyroid function (thyrotropin ≤ 1×ULN).

You may not qualify if:

• Known microsatellite instability high (MSI-H) mCRC.
• Participation in another study with intervention or drugs within the past 4 weeks.
• Performing surgery and incomplete recovery within the past 4 weeks.
• Subjects with active autoimmune diseases or with related history. Subjects with controlled type I diabetes or hypothyroidism with substitution therapy may be included for further screening.
• Any conditions requiring corticosteroids (\> 10 mg per day of prednisone or equivalent) or immunosuppressive drugs as systemic treatment within the past 1 week.
• Other active malignancy within the past 5 years, except for the cured limited cancer (such as basal cell carcinoma, carcinoma in situ of the prostate or cervix, etc.).
• Subjects with history of hepatic encephalopathy or confirmed metastases to central nervous system.
• Subjects with non-infectious pneumonia under steroid treatment within the past 6 months.
• Suffering from chronic or active infections, fever (≥ 38.5℃) within the past 1 week, or white blood cell count \> 15×10\^9/L), requiring systemic anti-infective treatment at the screening period, except for viral hepatitis.
• Subjects with any other abnormal condition that is inconsistent with the study medication, or may increase the risk of the subject，according to investigators' judgment.
• Congenital or acquired immunodeficiency (such as human immunodeficiency virus).
• Subjects with active hepatitis B virus (HBV) (HBV surface antigen positive and HBV-DNA \> 2000 IU/ml) or hepatitis C virus (HCV) (HCV antibody and HCV-RNA positive).
• Subject who received a live attenuated vaccine within the past 4 weeks, or vaccination is planned during anti-PD-1 antibody treatment or within 5 months after the last treatment.
• More than mild pericardial effusion, massive pleural or/and peritoneal effusions need puncture and drainage at the screening period.
• Subjects with symptomatic heart and cerebrovascular diseases: heart failure (New York Heart Association class III or IV, left ventricular ejection fraction \< 50%), uncontrolled hypertension or arrhythmias, serious cardiovascular and cerebrovascular events (acute coronary syndrome, stroke, thromboembolism, etc.) within the past 6 months.

Sponsors & Collaborators

• China Medical University, China: lead

Study Sites (1)

Cancer Hospital of China Medical University/Liaoning Cancer Hospital &Institute

Shenyang, Liaoning, 110042, China

RECRUITING

Related Publications (1)

• Dong Q, Diao Y, Sun X, Zhou Y, Ran J, Zhang J. Evaluation of tyrosine kinase inhibitors combined with antiprogrammed cell death protein 1 antibody in tyrosine kinase inhibitor-responsive patients with microsatellite stable/proficient mismatch repair metastatic colorectal adenocarcinoma: protocol for open-label, single-arm trial. BMJ Open. 2022 Apr 4;12(4):e049992. doi: 10.1136/bmjopen-2021-049992.

  PMID: 35379611 DERIVED

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Study Officials

• Jingdong Zhang

  China Medical University, Liaoning Cancer Hospital & Institute,China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qian Dong

CONTACT

17309815028; dongqian08@163.comcom

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 23, 2020
• Study Start: July 24, 2020
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: October 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediately following publication.No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal. The proposals should be directed to jdzhang@cancerhosp-ln-cmu.com.

Locations

CN (1)