The Combination of Immunotherapy and Stereotactic Ablative Radiotherapy in MSS Oligometastatic Colorectal Cancer

NCT04535024 | Unknown Phase 2

• 1 other identifier: FDRT-2019-251-1881
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, single-arm phase II clinical trial. This study aims to evaluate the safety and tolerability of stereotactic ablative radiotherapy (SABR) in combination with Sintilimab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in patients with microsatellite stable (MSS) oligometastatic colorectal cancer. A total of 60 MSS oligometastatic colorectal cancer patients will be recruited and receive multisite SABR followed by immunotherapy of Sintilimab within one week from completion. Sintilimab will be given at a fixed dose of 200mg (100mg if weight \< 50 kg) via intravenous infusion on the first day of each cycle, repeated every three weeks. The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. The tumor regression, disease control, adverse events and long-term survival will be analyzed.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The percentage of patients with objective response in the non-irradiated metastatic lesions. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) and the immune related response criteria (iRECIST) after treatment.

  Up to 2 years

Secondary Outcomes (5)

• Disease Control Rate

  Up to 2 years

• Duration of Response

  Up to 2 years

• Progression-Free Survival

  Up to 3 years

• Overall Survival

  Up to 3 years

• Acute Toxicity

  Up to 2 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

A total of 60 MSS oligometastatic colorectal cancer patients will receive multisite SABR followed by Sintilimab within one week from completion. The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal.

Radiation: Stereotactic Ablative Radiotherapy (SABR); Drug: Sintilimab

Interventions

Stereotactic Ablative Radiotherapy (SABR) RADIATION

We plan to irradiate as many metastatic lesions as possible, in the precondition that normal tissues can tolerate. Target dose will be adjusted depending on site of the lesion and organs at risk (BED \> 100Gy). Treatment schedule is once per day and five days per week. Sequence of irradiation for multiple metastases is at the discretion of the investigators based on their experience.

Treatment Arm

Sintilimab DRUG

Starts within one week upon SABR completion: 200mg, d1, q3w; Continued until disease progression, unacceptable toxicity or patient withdrawal.

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70 years old, regardless of gender
• Fully informed and willing to provide written informed consent for the trial
• ECOG performance status 0-1
• Has an investigator determined life expectancy of at least 6 months
• Histologically confirmed colorectal adenocarcinoma, with MSS or pMMR status
• Has 2-5 measurable metastatic lesions detected on imaging, with none of them indicated for surgery; or the participant refuses to receive surgery. Biopsy of metastasis is preferred, but not required
• Has undergone at least one dose of first-line systemic chemotherapy, except for any type of immunotherapy
• Multiple sites of lesions can be safely treated by SABR, and at least one lesion spared from irradiation, so as for assessment. The maximum diameter of each lesion for irradiation is no more than 5cm.
• Demonstrate adequate organ function
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

You may not qualify if:

• Pregnant or lactating women
• Serious medical comorbidities precluding radiotherapy
• Prior radiotherapy to a site requiring treatment
• Malignant pleural effusion
• Inability to treat all sites of active disease
• Has clinical or radiologic evidence of spinal cord compression or tumor within 3mm of spinal cord on MRI.
• Dominant brain metastasis requiring surgical decompression
• Has prior treatment with cancer immunotherapy including, but not limited to immune checkpoint inhibitors.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of \>10 mg Prednisone daily or equivalent at time of trial treatment.
• Has a known history of active Bacillus Tuberculosis
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Hypersensitivity to PD-1 inhibitor or any of its excipients.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered from adverse events due to a previously administered agent.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sintilimab

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

Study Officials

• Zhen Zhang, MD, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, MD, PhD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

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: August 27, 2020
• First Posted: September 1, 2020
• Study Start: March 4, 2021
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 11, 2021

Record last verified: 2021-05

Locations

CN (1)