Second-line Surufatinib Combined With Chemotherapy in Advanced CRC

Phase 2

• Conditions: Advanced Colorectal Cancer
• Interventions: Drug: Surufatinib(HMPL-012)

• Registration Number: NCT04734249
• Lead Sponsor: Fujian Cancer Hospital

Brief Summary

A phase II, muti-cohort study to assess the efficacy and safety of Surufatinib combined with chemotherapy as a second-line treatment in patients with advanced CRC

Detailed Description

This study adopt Simon's two-stage minimax designs method based on the primary endpoint of objective response rates. In each arm, 15 patients were planned for the first stage. If two or more responses were observed, an additional 13 patients were to be accrued for a total of 28 patients. If 7 or more of the 28 patients in an arm achieved an objective response, then that arm was designated worthy of additional investigation.

Surufatinib will be orally administered within 1 hour after breakfast once a day (QD) , Cohort 1 :Surufatinib+mFOLFOX6/FOLFIRI,Cohort 2 :Surufatinib+FOLFOXIRI for every 14-day treatment cycle until disease progression, death, intolerable toxicity or other protocol specified end-of-treatment criteria is met (which comes first).

Study Timeline

• Status Verified: 2021-01
• Study First Submitted: 2021-01-28
• Study First Submitted QC: 2021-01-31
• Last Update Submitted: 2021-01-31
• Study First Posted: 2021-02-02
• Last Update Posted: 2021-02-02
• Study Start: 2021-03
• Primary Completion: 2021-03
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Treatment with any of the following:

   1. Prior treatment with Surufatinib .
   2. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
   3. 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.

2. Patients with other malignancies, except basal cell carcinoma and carcinoma in situ..

3. 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.

4. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 2 weeks prior to start of study treatment.

5. 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.

6. 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.

7. Any of the following cardiac criteria:

   1. 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).
   2. 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).
   3. 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.
   4. Left ventricular ejection fraction (LVEF) ≤ 40%.

8. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease.

9. Women who are breastfeeding or have a positive urine or serum pregnancy test at the Screening Visit.

10. History of hypersensitivity to any active or inactive ingredient of Surufatinib or to drugs with a similar chemical structure or class to Surufatinib.

11. Patients who are allergic to paclitaxel or other drugs prepared with polyoxyethyl castor oil, carboplatin or other platinum containing compounds.

    Patients with contraindications of Chemotherapy .

12. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

13. Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Advanced CRC	Surufatinib(HMPL-012)	Patients with Advanced CRC were given Surufatinib Combined With Chemotherapy

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	up to 12 months	CR + PR rate according to the RECIST version 1.1 guidelines.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	up to 12 months	To assess the efficacy of Surufatinib Combined With Chemotherapy as second-line therapy to Advanced CRC, patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Overall survival time	up to 36 months	OS was calculated from the date of pharmacy to death from any cause.
Assess the anti-tumor activity:DCR	up to 12 months	Disease control rate (DCR):CR + PR + SD rate according to the RECIST version 1.1 guidelines.