Clinical trial NCT04625894: The Combination of Immunotherapy and Stereotactic Ablative Radiotherapy in Oligometastatic Gastrointestinal Cancer
Official title: Phase I Clinical Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Camrelizumab in Patients With Oligometastatic Gastrointestinal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Oligometastatic Gastrointestinal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-11-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-center, open-label, single-arm phase I clinical study to exploratory observe and evaluate the efficacy and safety of anti-PD-1 antibody (Camrelizumab for Injection) combined with multisite stereotactic ablative radiotherapy (SABR) in patients with oligometastatic gastrointestinal cancer.

According to the origin site of metastases, this study will consist of three subgroups, including gastric carcinoma group, colorectal carcinoma group and hepatocellular carcinoma group. For each of the subgroup, seven eligible patients with oligometastatic cancer originating from stomach, colon and liver, respectively will be recruited. All patients will receive multisite SABR followed by immunotherapy of Camrelizumab within one week from completion. Camrelizumab will be administered at a fixed dose of 200 mg intravenously (iv) on D1 in a 14-day cycle. The treatment will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal.

Tumor tissue samples, sections, paraffin blocks or biopsy blocks, and biomarkers, including but not limited to PD-L1 expression level and the proportion of positive cells, TMB level and MMR status, will be collected from subjects.


Eligibility criteria: Inclusion Criteria:

1. Aged 18-70 years old, regardless of gender;
2. Fully informed and willing to provide written informed consent for the trial;
3. ECOG performance status 0-1;
4. Expected survival time ≥ 6 months;
5. Has gastric carcinoma /colorectal carcinoma / hepatocellular carcinoma, confirmed by histopathology (or pathology consultation in our hospital) and measurable oligometastatic lesions on imaging (RECIST version 1.1); pathological diagnosis confirmation of oligometastatic lesions using biopsy tissue samples (e.g. obtained by hollow core needle, biopsy, excision, etc.) is recommended but not required;
6. Has undergone curative treatment on the primary lesion at least three months ago, without local progression;
7. Has received standard treatment prior to enrolment, except for any type of immunotherapy;
8. Has no more than three metastatic lesions detected on imaging in single organ (e.g. lung, liver, brain, bone, etc.), and the total number of metastases is no more than five;
9. Multiple sites of lesions can be safely treated by SABR; and the maximum diameter of each lesion for irradiation is no more than 5cm.
10. Contraindicated for surgery or the participant refuses to receive surgery.
11. Has adequate organ function to tolerate the regimen:
12. Bone marrow function: neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L;
13. Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal; AST and ALT ≤ 2.5 times the upper limit of normal or the presence of liver metastasis ≤ 5 times the upper limit of normal; total bilirubin ≤ 1.5 times the upper limit of normal, or patients with Gilbert's syndrome ≤ 2.5 times the upper limit of normal;
14. 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
15. Non-lactating patients.

Exclusion Criteria:

1. Pregnant or lactating women
2. Serious medical comorbidities precluding radiotherapy
3. Prior radiotherapy to a site requiring treatment
4. Malignant pleural effusion
5. Inability to treat all sites of active disease
6. Has clinical or radiologic evidence of spinal cord compression or tumor within 3mm of spinal cord on MRI.
7. Dominant brain metastasis requiring surgical decompression
8. Has prior treatment with cancer immunotherapy including, but not limited to immune checkpoint inhibitors.
9. 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.
10. Has a known history of active Bacillus Tuberculosis
11. Has active autoimmune disease that has required systemic treatment in the past 2 years
12. Hypersensitivity to PD-1 inhibitor or any of its excipients.
13. 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.

Primary outcomes:
measure: Dose-limiting toxicities (DLT)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Adverse events (AEs)
timeFrame: Up to 2 years
measure: Local control (LC)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Quality of life assessment
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: