Fruquitinib Combined With Camrelizumab in Non MSI-H/dMMR Refractory Colorectal Cancer

July 20, 2022 updated by: The First Affiliated Hospital with Nanjing Medical University

A Single Arm, Open Label, Phase II, Exploratory Study of Fruquitinib Combined With Camrelizumab in Non MSI-H / dMMR Refractory Colorectal Cancer.

Limited agents are optional after standard first and second line treatment for mCRC. Nowadays, cancer therapy has entered the era of immunotherapy. The approved cancer therapies include pembrolizumab and nivolumab, but only for MSI-H patients. 95% of non MSI-H / dMMR patients with advanced colorectal cancer can not benefit from them. Therefore, the use of PD-1 / PD-L1 monoclonal antibody in mCRC is greatly limited. Our previous research showed that anti-PD-1 combined with Fruquintinib can significantly inhibit the growth of CRC in MSS mice. At the same time, a retrospective clinical study showed that patients with MSS CRC can benefit from Sintilimab combined with Fruquintinib. Camrelizumab is PD-1 monoclonal antibody, which has been approved for a variety of tumors. The prospective clinical trial of Camrelizumab combined with Fruquintinib may bring new hope for the treatment of non MSI-H / dMMR patients with mCRC.This study is aimed to explore the efficacy, safety in advanced colorectal cancer failed to standard therapy in Chinese population.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Our previous research showed that anti-PD-1 combined with Fruquintinib can significantly inhibit the growth of CRC in MSS mice. At the same time, a retrospective clinical study showed that patients with MSS CRC can benefit from Sintilimab combined with Fruquintinib. Camrelizumab is PD-1 monoclonal antibody, which has been approved for a variety of tumors. The prospective clinical trial of Camrelizumab combined with Fruquintinib may bring new hope for the treatment of non MSI-H / dMMR patients with mCRC.This study is aimed to explore the efficacy, safety in advanced colorectal cancer failed to standard therapy in Chinese population.

Study Type

Interventional

Enrollment (Anticipated)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • The First Affiliated Hospital of Nanjing Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
  • Subjects with non MSI-H / dMMR metastatic colorectal cancer(CRC) (Stage IV)
  • Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan.
  • Subjects must not have been treated with Fruquitinib or any anti-PD-1 inhibitors.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary.
  • Adequate bone marrow, liver, cardiac and renal function as assessed by the laboratory required by protocol.
  • Assigned informed consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
  • Life expectancy of at least 3 months.
  • Subjects must complete the treatment and follow-up on schedule according to the research plan.
  • No brain metastasis, no spinal cord compression.
  • Subjects agree to use blood samples for study analysis.
  • Women of childbearing age must be negative in pregnancy test and willing to take effective contraceptive measures during the study period.

Exclusion Criteria:

  • Subjects are severe malnutrition or need tube feeding.
  • Radiotherapy or surgery has been performed within 30 days before treatment.
  • Previous treatment with anti-PD-1 / PD-L1 inhibitor and / or fruquitinib.
  • Other malignant tumors within 2 years and without cure (except for cured basal cell carcinoma of skin and carcinoma in situ of cervix);
  • Subjects have active autoimmune system diseases、systemic hormone therapy or anti autoimmune drug therapy.
  • Subjects with immunodeficiency or receiving systemic steroid therapy (prednisone > 10 mg / day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days before the first dose of combination therapy in this study;
  • Subjects with active infection and still need systemic treatment 7 days before the first dose of therapy in this study.
  • Subjects with uncontrollable systemic diabetes.
  • Subjects with interstitial lung disease, non infectious pneumonia or pulmonary fibrosis;
  • Subjects who have received allogeneic organ or stem cell transplantation in the past.
  • Subjects allergic to the drugs or related components involved in this study.
  • Are participating in other interventional clinical studies.
  • The previous anti-tumor related adverses do not return to grade 1 in CTCAE before the first combination therapy.
  • Subjects who have uncontrolled hypertension by drugs, that is, systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg.
  • Thrombotic or hemorrhagic tendency or history within 60 days before the first medication, regardless of the severity.
  • Any serious or unstable medical condition、mental illness or known active alcohol or drug abuse or dependence.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Combination of Fruquintinib and Camrelizumab
Fruquintinib 5mg d1-21+ Camrelizumab 200mg d1; Repeated every 4 weeks
Drug: Combination of Fruquintinib and Camrelizumab
Fruquintinib 5mg d1-21+Camrelizumab 200 mg d1
Other Names:
  • Fruquintinib 5mg d1-21+Camrelizumab 200 mg d1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate(ORR)
Time Frame: up to 2 years
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival(PFS)
Time Frame: From date of subjects until the date of first documented progression or death from any cause, whichever came first, assessed up to 24 months
PFS was defined as the time from assignment to disease progression radiological/clinical or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.
From date of subjects until the date of first documented progression or death from any cause, whichever came first, assessed up to 24 months
Overall Survival (OS)
Time Frame: From assignment of the first subject until 32 death events observed, up to 2 years.
OS is defined as the time from date of assignment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
From assignment of the first subject until 32 death events observed, up to 2 years.
Disease control rate (DCR)
Time Frame: up to 2 years
DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD)
up to 2 years
Tumor Mutation Burden (TMB)
Time Frame: up to 2 years
The total number of somatic gene coding error, base substitution. gene insertions or deletions in every million base detected.
up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
immunocytes and cell factor
Time Frame: up to 2 years
The concentration of immunocytes and cell factor in the blood of patients.
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Study Chair: Rui Wang, The First Affilated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 26, 2021

Primary Completion (ANTICIPATED)

June 1, 2024

Study Completion (ANTICIPATED)

June 1, 2024

Study Registration Dates

First Submitted

March 28, 2021

First Submitted That Met QC Criteria

April 27, 2021

First Posted (ACTUAL)

April 30, 2021

Study Record Updates

Last Update Posted (ACTUAL)

July 25, 2022

Last Update Submitted That Met QC Criteria

July 20, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KEEP-G 05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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