Clinical trial NCT03921684: Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients
Official title: Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Nivolumab
Chemoradiation
mFOLFOX6
rectal cancer
Anti-PD-1 antibody
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-04-19
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II, prospective, open label, one-center study for evaluation of the addition of nivolumab to the chemotherapy phase of the neoadjuvant treatment for locally advanced rectal cancer patients. Subjects must have received no prior treatment for rectal cancer (chemotherapy, radiotherapy or surgery) and no prior treatment with checkpoint inhibitors.

Eligible subjects will receive chemoradiation for a period of 5 weeks, 6 cycles of chemo-immunotherapy (mFOLFOX6 + nivolumab) for a period of 12 weeks, once every 2 weeks, and will undergo surgery after 4 weeks.


Eligibility criteria: Inclusion Criteria:

* Signed written IRB approved informed consent
* Age ≥ 18 years
* ECOG PS 0-1
* Subjects with histologically confirmed primary (non-recurrent) locally advanced rectal adenocarcinoma
* Stage T3-4 N0 or TX N+ according to baseline rectal EUS and PET-CT
* Patients who are planned for neoadjuvant chemoradiation and are surgical candidates
* No prior chemotherapy, radiotherapy or surgery for rectal cancer
* No prior radiotherapy to the pelvis, for any reason
* Presence of adequate contraception in fertile patients
* Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug
* Women must not be breastfeeding
* Ability to swallow tablets
* No previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin

Exclusion Criteria:

* Active autoimmune disease. \[Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll\]
* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* Pregnancy or breastfeeding

Primary outcomes:
measure: pathological complete response (pCR) rate
timeFrame: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
measure: Incidence of Treatment-Emergent Adverse Events (Safety)
timeFrame: Time from screening until the end of study drug administration, assessed up to 24 months
Secondary outcomes:
measure: Disease Free Survival (DFS)
timeFrame: Time from the first day of treatment to the first event of: loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death from any cause, assessed up to 42 months
measure: Overall Survival (OS)
timeFrame: The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
Study officials:
affiliation: Rabin Medical Center
name: Baruch Brenner, Prof
role: PRINCIPAL_INVESTIGATOR
References: