Anlotinib Plus Sintilimab as First-line Treatment for Patients With Advanced Colorectal Cancer (APICAL-CRC)

April 22, 2024 updated by: Yuan-Sheng Zang, Shanghai Changzheng Hospital

Anlotinib Plus Sintilimab as First-line Treatment for Patients With Advanced Colorectal Cancer (APICAL-CRC): a Single Center, Single-arm Phase II Study (APICAL-CRC)

This study is designed to evaluate the efficacy and safety of the combination of Anlotinib and Sintilimab in advanced colorectal cancer as first-line treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Sintilimab is a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), thereby blocking the interaction of PD-1 with its ligands (PD-L1 and PL-L2) and consequently helping to restore the endogenous antitumour T-cell response. In the present study, we design a single-arm, single center Phase II trial to evaluate the efficacy and safety of the combination of Anlotinib and Sintilimab in advanced colorectal cancer as first-line treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • China
      • Shanghai, China
        • Department of Medical Oncology, Shanghai Changzheng Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  • Patients have histologically or cytologically confirmed advanced or recurrent CRC;
  • No prior systematic anti-cancer treatment and relapse or metastases was occurred more than 12 months after adjuvant chemotherapy;
  • Patients have measurable disease as defined by RECIST 1.1 as determined by investigator;
  • Patient with a history of radiotherapy at least 3 months before on the day of providing consent, but the measurable lesion should not be within the scope of radiotherapy;
  • Patients with age of 18-75yr;
  • Patients with a performance status of 0,1or 2 on the Eastern Cooperative Oncology Group.；
  • Patients with Life expectancy of more than 12 weeks;
  • Patients must have the ability to understand and sign the written informed consent voluntarily;
  • Female of childbearing potential who are negative in a pregnancy test within 7 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, a contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment.

Exclusion criteria

  • Patients with dMMR/MSI-H;
  • Patients with major surgery or severe trauma within 4 weeks before the first medication;
  • Patients with hypersensitivity to the components in the study protocol;；
  • Patients who are ready to give birth or are pregnant;
  • Patients with brain metastases who are unable to accurately describe the condition;
  • Patients received immune-suppressive drugs 2 weeks before initial treatment (inhaled cortisol or other steroid hormones≤10 mg/day prednisone or equivalent pharmacophysiologic doses were excluded);
  • Planned live attenuated vaccine within 4 weeks prior to or during study treatment;
  • Patients have received anlotinib or anti-PD-1 monoclonal antibody therapy or other therapies that act on T-cell co-stimulation targets or checkpoints;
  • Within 6 months prior to the start of study treatment, the following diseases appeared: myocardial infarction, severe/unstable angina, NYHA grade 2 or above congestive heart failure, poorly controlled arrhythmias, etc;
  • Active hepatitis;

  • Bone marrow, liver and kidney function did not meet the requirements of chemotherapy as follows:

    • Neutrophil count<1,500/mm3;
    • Platelet count <80,000/mm3;
    • Total bilirubin >1.5-times the upper limit of normal;
    • ALT/AST>2.5-times the upper limit of normal for patients without liver metastases; (5.0-times the upper limit of normal for patients with liver metastases)
    • Creatinine >1.5-times the upper limit of normal;
  • Patients with cancers other than advanced colorectal cancer within five years prior to the start of treatment in this study. Cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor were excluded;
  • History of substance abuse, drug use, alcohol dependence;
  • Patients without legal capacity or limited civil capacity;
  • Patients with autoimmune diseases or organ transplantation;
  • Other situations that the investigator deemed inappropriate for enrollment;

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Anlotinib and Sintilimab
the combination of Anlotinib with Sintilimab as first-line treatment
Drug: Anlotinib plus Sintilimab
Anlotinib 12mg oral administration daily d1-d14, q3w; Sintilimab 200mg iv drop d1, q3w

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objecitve response rate
Time Frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission
Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progress Free Survival
Time Frame: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks
Time from treatment beginning until disease progression
Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks
Overall Survival
Time Frame: From date of treatment beginning until the date of death from any cause, through study completion, an average of 3 weeks
Time from treatment beginning until death from any cause
From date of treatment beginning until the date of death from any cause, through study completion, an average of 3 weeks
Incidence of Treatment-related adverse Events
Time Frame: Through study completion, an average of 3 weeks
Through study completion, an average of 3 weeks
Deepness of response
Time Frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Investigation of depth of response during first-line treatment
Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Disease control rate
Time Frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Proportion of patients who achieved a complete response, a partial response, or stable diseas
Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanghai Changzheng Hospital

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 29, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 14, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 17, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APICAL-CRC

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

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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