Radiotherapy in Combination With Sintilimab，GM-CSF and Fruquintinib in Patients With MSS mCRC

NCT05292417 | Unknown Phase 2

• 1 other identifier: Caimingquan
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the clinical efficacy and safety of hypofractionation radiotherapy combined with sintilimab，GM-CSF and Fruquintinib in Patients With MSS Metastatic Colorectal Carcinoma (mCRC)

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Defined as the time from the date of the first dose of treatment to the date of the first documentation of disease progression or death, whichever occurs first. Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST

  2 years

Secondary Outcomes (5)

• Objective response rate

  1 year

• Disease Control Rate（DCR）

  1 year

• Duration of Response(DOR)

  1 year

• Overall survival (OS)

  2 years

• Safety:Percentage of Participants With Adverse Events (AEs)

  Up to 30 days after the last cycle of per-protocol treatment and 90 days after last dose of treatment

Study Arms (1)

Experimental Group

EXPERIMENTAL

hypofractionation radiotherapy combined with sintilimab,GM-CSF and Fruquintinib in the third-line or above treatment of MSS Metastatic Colorectal Carcinoma(mCRC)

Radiation: hypofractionation Radiotherapy; Drug: sintilimab; Drug: GM-CSF; Drug: Fruquintinib

Interventions

hypofractionation Radiotherapy RADIATION

Patients will receive radiation to the target lesion at a dose of 5Gy, 5 fractions a week, or a dose of 8Gy, 3 fractions a week. The course last once or twice depending on the investigator.

Also known as: Radiotherapy

Experimental Group

sintilimab DRUG

200 mg per IV infusion every 21 days until disease progression or participant withdrawal from study or last for two years

Also known as: IBI308

Experimental Group

GM-CSF DRUG

200µg given 7-14 days(until WBC≥40x109/L), every 21 days until disease progression or participant withdrawal from study or last for two years.

Also known as: Human Granulocyte

Experimental Group

Fruquintinib DRUG

Fruquintinib will be given 5mg qd for 2 weeks on and 1 week off, Q3W.

Also known as: Elunate

Experimental Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Assigned informed consent
• Age: 18-80 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3
• Histological or cytological documentation of adenocarcinoma of the colon or rectum MSS metastatic colorectal cancer(CRC) checked by IHC or PCR.
• Patients must have failed at least two lines of prior treatment
• Patients must have not previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
• Patients must have not previously received Fruquintinib.
• Life expectancy of at least 3 months
• At least 1 measurable disease according to Response Evaluation Criteria in Solid --Tumors (RECIST) criteria, version 1.1.is necessary.
• Controlled hypertension.
• Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol.
• Women of childbearing age must be negative in pregnancy test. Fertile female and male patients agree to use effective contraceptive methods during the study and within 6 months post to the last dose, such as double barrier contraception, condoms, oral or injection contraceptives, intrauterine devices, abstinence, etc. All female patients will be considered fertile unless the female patient has natural menopause or has undergone artificial menopause or sterilization (hysterectomy, bilateral appendage resection).

You may not qualify if:

• Patients with MSI-H / dMMR metastatic colorectal cancer(CRC);
• Uncontrollable malignant pleural effusion, ascites or pericardial effusion (defined as ineffectively controlled by diuresis or puncture drainage judged by investigators);
• Clinically significant abnormal electrolyte abnormality as judged by investigators;
• Clinically significant liver disease, including active viral hepatitis \[HBsAg and/or HbcAb is positive and HBV (hepatitis B virus) DNA \> 10000 copies/ mL or \> 2000 IU/mL; HCV (hepatitis C virus) antibody positive and HCV RNA \> 1000 copies/ mL\], or other active hepatitis, clinically significant moderate to severe cirrhosis;
• Central nervous system (CNS) metastasis in previous or screening is excluded ,except CNS without clinical symptom or stable period ≥4 weeks after treatment ;
• Patients with evidence or history of propensity to hemorrhage within 3 months prior to first dosing, regardless of severity(such as melena, hematemesis, hemoptysis, bloody stools）；
• History of arterial thrombosis within 6 months; Patients with history of deep vein thrombosis (DVT) are eligible as long as they have received or are receiving appropriate anticoagulation therapy.
• Uncontrolled hypertension. (Systolic blood pressure 150 mmHg or diastolic pressure 90 mmHg despite optimal medical management).
• Radical radiotherapy within 4 weeks prior to first dosing;
• Patients have dysphagia;
• History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of the lung function, etc., which may interfere with the detection and treatment of suspected drug-related lung toxicity, except radiation pneumonitis in the radiation treatment area;
• Confirmed human immunodeficiency virus (HIV) infection or confirmed syphilis; Patients have high risk of bleeding events such as unhealed wounds, ulcers, fractures,or. patients have active ulcer of stomach and duodenum, ulcerative colitis and other digestive tract diseases or unresectable tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation, as judged by investigators;
• The adverse events due to previous anti-tumor therapy has not recovered to ≤ CTCAE Grade 1, except alopecia and peripheral neurotoxicity with ≤ CTCAE grade 2 caused by platinum chemotherapy;
• Patients with active infection and still need systemic treatment;
• Steroids (more than 10 mg/day prednisone or other equivalent hormones) or other immunosuppressive agents for systemic therapy within 4 weeks prior to first dosing, except nasal spray, inhaled or other topical use of steroid (i.e. no more than 10mg/day prednisone or equivalent doses of other corticosteroids);

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Study Sites (1)

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361000, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiation Dose Hypofractionation; Radiotherapy; sintilimab; Granulocyte-Macrophage Colony-Stimulating Factor; HMPL-013

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Therapeutics; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Mingquan Cai

  The First Affiliated Hospital of Xiamen University

  PRINCIPAL INVESTIGATOR

• Xiyi Liao

  The First Affiliated Hospital of Xiamen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mingquan Cai

CONTACT

15395923893; mingquan035@163.com

Xiyi Liao

CONTACT

860592-2137252; liaodoctor@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 23, 2022
• Study Start: March 25, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)