PD-1 Inhibitors Combined With VEGF Inhibitors for Locally Advanced dMMR/MSI-H Colorectal Cancer

NCT04715633 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: B2020-120-03
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

In this open-label phase II study, patients will be scheduled for neoadjuvant treatment with PD-1 inhibitors (Camrelizumab) plus VEGF inhibitor (Apatinib) for dMMR/MSI-H colorectal cancer staged as locally advanced (cT3-4N+/-M0 for rectal cancer, cT4 or cT3 with extramural extension ≥5mm for colon cancer). Radiological evaluation will be preformed after 4 cycles of treatment. Patients (either with colon or rectal cancer) who achieve complete clinical response will be offered the choice of Watch \& Wait.

Conditions

Colorectal Cancer; Microsatellite Instability High

Outcome Measures

Primary Outcomes (1)

• Clinical complete response or pathological complete response

  Clinical complete response or immunotherapy-related pathological complete response (cCR or immunotherapy-related pCR)

  up to 2 year

Secondary Outcomes (5)

• Objective Response Rate (ORR, PR+CR)

  up to 2 year

• 3-year relapse-free survival

  up to 3 years

• 3-year overall survival

  up to 3 years

• Surgical complications

  within 1 month after surgery

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  up to 2 year

Study Arms (1)

PD-1 inhibitors plus VEGF inhibitors

EXPERIMENTAL

Patients will be given 4 cycles of Camrelizumab (200mg iv every 3 weeks) plus Apatinib (250mg QD day1-14) before being evaluated for response.

Drug: PD-1 inhibitor plus VEGF inhibitors

Interventions

PD-1 inhibitor plus VEGF inhibitors DRUG

Camrelizumab 200mg IV every 3 weeks; Apatinib 250mg QD day 1-14. Rescue chemotherapy: Oxaliplatin 130mg/m2 IV drip Q3W d1+Capecitabine 1000mg/m2 QD d1-d14 Rescue chemoradiotherapy: Long-course radiotherapy +Capecitabine 825mg/m2 QD d1-d14

Also known as: Camrelizumab plus Apatinib

PD-1 inhibitors plus VEGF inhibitors

Eligibility Criteria

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

You may qualify if:

• Locally confirmed dMMR or MSI-H colorectal carcinoma
• Tumor staging based on CT/MR or transrectal ultrasound imaging:
• Colon cancer: radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm with or without lymph node involvement)
• Rectal cancer: \<12 cm from the anal verge and radiological high risk (rT3/4 with or without lymph node involvement)
• No sign of bowel obstruction, or bowel obstruction has been relieved by ostomy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
• Aged 18 or over
• Life expectancy of at least 2 years
• Measurable disease
• Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose
• Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose
• Adequate organ function

You may not qualify if:

• Active autoimmune disease that has required systemic treatment in past 2 years
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to this study start
• Currently participating and receiving treatment in another study within 4 weeks of study start
• History of severe allergic reaction to monoclonal antibody
• Strong evidence of distant metastases or peritoneal nodules (M1)
• Colonic obstruction that has not been defunctioned
• Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death \[PD\]-1, anti-PD ligand 1 \[L1\], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\] agent, etc.) or anti-VEGF agents (e.g., Bevacizumab, Apatinib)
• Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk \<5%
• Received a live vaccine within 30 days of planned start of study medication
• Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
• Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
• Known history of active tuberculosis (Bacillus tuberculosis \[TB\])
• Active infection requiring systemic therapy

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Guangdong Provincial People's Hospital: collaborator
• Guangdong Provincial Hospital of Traditional Chinese Medicine: collaborator

Study Sites (1)

651 Dongfeng Road East

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Yu JH, Xiao BY, Li DD, Jiang W, Ding Y, Wu XJ, Zhang RX, Lin JZ, Wang W, Han K, Kong LH, Zhang XK, Chen BY, Mei WJ, Pan ZZ, Tang JH, Zhang XS, Ding PR. Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study. Lancet Oncol. 2024 Jul;25(7):843-852. doi: 10.1016/S1470-2045(24)00203-1. Epub 2024 Jun 6.

  PMID: 38852601 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Immune Checkpoint Inhibitors; camrelizumab; apatinib

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)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Pei-Rong Ding, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 20, 2021
• Study Start: December 1, 2020
• Primary Completion: August 30, 2023
• Study Completion: July 31, 2025
• Last Updated: July 9, 2024

Record last verified: 2024-07

Locations

CN (1)