Surufatinib Combine With Immunotherapy and Chemotherapy for Second-line Treatment in Advanced Colorectal Cancer

NCT04929652 | Unknown Phase 1

• 1 other identifier: HMPL-012-SPRING-C102/JS-GI2101
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

Brief Summary

The objective is to investigate the efficacy and safety of Surufatinib Combine With Immunotherapy and Chemotherapy for Second-line Treatment in Advanced Colorectal Cancer.

Conditions

Advanced Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerable Dose (MTD)

  Usually refers to the highest dose at which a subject's probability of developing DLT does not exceed the probability of target toxicity during the regime-specified DLT observation period.

  up to 12 months

• Objective response rate (ORR)

  CR + PR rate according to the RECIST version 1.1 guidelines.

  up to 12 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  up to 12 months

• Overall survival time

  up to 36 months

• Assess the anti-tumor activity:DCR

  up to 12 months

Study Arms (1)

Advanced CRC

EXPERIMENTAL

Patients with Advanced CRC were given Surufatinib Combine With Immunotherapy and Chemotherapy.

Drug: Surufatinib,Camrelizumab,Irinotecan,GM-CSF

Interventions

Surufatinib,Camrelizumab,Irinotecan,GM-CSF DRUG

1. Dose climbing stage design (n=12) : Surufatinib: Oral, 3w.The initial dose of 250mg/ day (n=6) : If 2 out of 6 patients developed \> DLT in the first treatment cycle, the exploratory dose was 200 mg/ day; if ≤2 out of 6 patients developed DLT, the exploratory dose was 300mg/ day (n=6);At the next dose phase, if 2 out of 6 patients with \> developed DLT, the previous dose was recommended or the study was terminated;If no more than 2 out of 6 patients developed DLT, the dose was the recommended dose；PD-1,200mg, iv,D1, 3w；Irinotecan: 200mg/㎡, iv, D1, 3w；GM-CSF,D2, D3, D4, D5, D6 and D7 in the first week of each cycle ； 2. Dose expansion phase design(n=36): 1. Surufatinib: Oral, 3w. the dose was set according to the recommended dose in the dose climbing stage; 2. PD-1(Camrelizumab) : 200mg, iv,D1, 3w; 3. Irinotecan: 200mg/㎡, iv, D1, 3w; 4. GM-CSF: continuous administration of D2, D3, D4, D5, D6 and D7 in the first week of each cycle, 5ug/kg once per body weight, once a day, 3w.

Also known as: Chemotherapy(Irinotecan),Immunotherapy(Camrelizumab,GM-CSF)

Advanced CRC

Eligibility Criteria

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

You may qualify if:

• Provision of written Informed Consent Form (ICF) prior to any study specific procedures.
• Male or female, age18-75 years.
• Pathologically confirmed unresectable locally advanced or advanced metastatic colorectal cancer .
• First-line use of oxaliplatin in combination with fluorouracil, whether or not combined with macromolecular targeted agents (Cetuximab or Bevacizumab);
• At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumour assessment scans are done at least 14days afar the screening biopsy is performed.
• The patient had previously failed standard first-line systemic chemotherapy,Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) if 6 months or more have passed since completion of therapy(Previous standard treatment did not include small molecule inhibitors of anti-angiogenesis and Immunotherapy for PD-1 and PD-L1).
• A WHO performance status equal to 0-1 and a minimum life expectancy of 12 weeks.
• Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values:
• Absolute neutrophil count (ANC) ≥1.5×109/L
• Platelet count ≥100×109 / L
• Hemoglobin≥9 g/dL
• Albumin≥3g/dL
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN if no demonstrable liver metastases or ≤ 5 × ULN in the presence of liver metastases.
• Total bilirubin (TBL)≤ 1.5 × ULN if no liver metastases or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.
• Creatinine≤ 1.5 × ULN concurrent with creatinine clearance ≤50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is ≤1.5 × ULN.

You may not qualify if:

• Treatment with any of the following:
• Prior treatment with Surufatinib and other small molecule antiangiogenic targeted drug therapy;.
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
• Radiotherapy with a limited field of radiation for palliation within 4 week of the first dose of study drug, with the exception of patients receiving radiation to \> 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
• First line treatment with irinotecan.
• Previous experience with other anti-PD-1 antibody therapy or other PD-L1 immunotherapy;
• Patients with other malignancies, except basal cell carcinoma and carcinoma in situ..
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
• Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 2 weeks prior to start of study treatment.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes it undesirable for the patient to participate in the trial OR which would jeopardize compliance with the protocol such as active infection. Screening for chronic conditions is not required.
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to swallow the study drug, or previous significant bowel resection that would preclude adequate absorption of Surufatinib.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \> 250 ms).
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead

Study Sites (5)

Changzhou NO.2 People's Hospital

Changzhou, Jiangsu, China

NOT YET RECRUITING

Jiangsu Cancer Institute & Hospital

Nanjing, Jiangsu, 210009, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

NOT YET RECRUITING

Wuxi People's Hospital

Wuxi, Jiangsu, China

NOT YET RECRUITING

Yangzhou First People's Hospital

Yangzhou, Jiangsu, China

NOT YET RECRUITING

MeSH Terms

Interventions

surufatinib

Study Officials

• Liangjun Zhu

  Jiangsu Cancer Institute & Hospital

  STUDY CHAIR

Central Study Contacts

Liangjun Zhu

CONTACT

+8613770575447; zhulj98@foxmail.com

Sheng Li

CONTACT

+8613770768636; lihsh198@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ward Director of Internal Medicine

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 18, 2021
• Study Start: June 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2024
• Last Updated: June 18, 2021

Record last verified: 2021-06

Locations

CN (5)