A phase Ib/II, multicenter study to investigate the safety, efficacy, and proof-of-concept (POC) of nivolumab monotherapy as a sequential therapy following preoperative chemoradiotherapy in patients with locally advanced resectable rectal cancer
- Conditions
- Rectal cancer
- Registration Number
- JPRN-UMIN000023148
- Lead Sponsor
- ational Cancer CenterHospital East
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 50
1.Pts who provided written consent for participation in the study
2.Treatment naive pts with rectal cancer in whom the inferior margin of the tumor was at a distance of 12cm or less from the AV before CRT
3.Primary rectal cancer histopathologically confirmed to be adenocarcinoma
4.Stage of T3,4 N any M0 before CRT
5.Macroscopic radical resection could be feasible, based on diagnostic imaging before CRT
6.Age of >=20 to<80 years
7.Pts with the PS 0 or 1
8.CRT meeting the following conditions has been administered:
Radiation at a dose of 45 Gy 25 fractions to the pelvic cavity and boost radiation at a dose of 5.4 Gy 3 fractions to the primary lesion
Capecitabine was started at a dose of 1650 mgm2 and administered in combination with radiation during a period equivalent to the half of 28 fractions irrespective of a dose reduction.
The last day of CRT is defined as the last day of radiotherapy. Oral administration of capecitabine is completed at the same time as the completion of radiation.
9.Pts with CRT associated AEs that recovered to Gre<=1 based on the CTCAE ver4 with regard to all items within 14 days after the end of CRT who are anticipated to receive nivolumab.
10.Pts without distant metastasis on the imaging test at the end of CRT.
11.Women of childbearing potential who consent to practicing contraception during the period from giving informed consent to 23weeks after the last dose of therapy.
12.Male pts who consent to practicing contraception during the period from giving informed consent to 31weeks after the last dose of the study drug.
13.Pts with adequate organ function meeting the following criteria at the time of enrollment;
Hgb>=9.0gdL
Neutro >=1500 mm3
Plt>=100000 mm3
PT INR<=1.5*ULN
Alb>=2.5 g/dL
TBil<=1.5*ULN
g.AST,ALT<=3.0*ULN
h.cre<=1.5 mgdL or creatinine clearance
>=45 mL min
1.Active multiple cancers .
2.Pts with recurrent rectal cancer.
3.Pts with a history of pelvic radiation.
4.Pts with a history of inflammatory bowel disease.
5.Pts with a history of pneumonitis or ILD.
6.Pts with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease.
7.Pts requiring treatment with systemic corticosteroids or immunosuppressants or who have received these treatments within 14 days before enrollment in the study.
8.Pts with a history of thyroid dysfunction.
9.Pts with a history or finding of cardiovascular risk falling into any of the following:
?left ventricular ejection rate below 50percent EF.
?history or finding of clinically significant, poorly controlled arrhythmia; exception: patients with well-controlled atrial fibrillation for more than 30 days before enrollment may be enrolled.
?history of acute coronary syndrome, coronary angioplasty, or stent placement within 6 months before enrollment.
?history or class II or more severe congestive heart failure according to NYHA .
?treatment-resistant hypertension.SP>140,DBP>90mmHG
?Pts wearing an implantable cardioverter defibrillator or permanent pacemaker.
10.Pts with poorly controlled diabetes mellitus or other diseases possibly interfering with toxicity evaluation.
11.Pts who are positive for any of the following: HIV-1and2 antibody,HTLV-1 antibody, HBs antigen,HCV antibody test.
HBV-DNA above detection sensitivity will be also excluded.
12.Pts who are pregnant or lactating or who may be pregnant.
13.Pts with significant unstable mental diseases or other medical diseases that may interfere with the safety of the subjects, obtaining informed consent, or compliance with the procedures for the clinical study.
14.history of treatment with nivolumab.
15.Pts who are not willing to or incapable of complying with the procedures specified in the protocol.
16.Pts cannot agree ICF.
17.Pts who are determined by the investigator to be unsuitable as a subject for the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pathological complete response (pCR) rate
- Secondary Outcome Measures
Name Time Method Objective Response rate(ORR)<br>Mode of recurrence<br>Disease-free survival(DFS) <br>Overall survival (OS)<br>Adverse event (AE)<br>Rate of completing the protocol herapy<br>Rate of radical resection<br>Macroscopic evaluation of (rectal cancer) resected specimen<br>Intraoperative safety evaluation <br>Postoperative safety evaluation