Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

Sponsor

Baruch Brenner (Other)

Overall Status

Recruiting

CT.gov ID

NCT03921684

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: Capecitabine Radiation: Radiation therapy Drug: mFOLFOX6 Drug: Nivolumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer

Anticipated Study Start Date :

Apr 1, 2019

Anticipated Primary Completion Date :

Apr 1, 2021

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant Treatment All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment	Drug: Capecitabine Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy Other Names: Xeloda Radiation: Radiation therapy 1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine Drug: mFOLFOX6 oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and fluorouracil 400 mg/m2 IV, fluorouracil 2400 mg/m2 IV (a 46 hrs CI), day 1 of each treatment cycle, every 2 weeks, given with nivolumab Drug: Nivolumab Nivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6 Other Names: Opdivo

Arm

Intervention/Treatment

Experimental: Neoadjuvant Treatment

All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment

Drug: Capecitabine

Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy

Other Names:

Xeloda

Radiation: Radiation therapy

1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine

Drug: mFOLFOX6

oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and fluorouracil 400 mg/m2 IV, fluorouracil 2400 mg/m2 IV (a 46 hrs CI), day 1 of each treatment cycle, every 2 weeks, given with nivolumab

Drug: Nivolumab

Nivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6

Other Names:

Opdivo

Outcome Measures

Primary Outcome Measures

pathological complete response (pCR) rate [Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months]
pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)
Incidence of Treatment-Emergent Adverse Events (Safety) [Time from screening until the end of study drug administration, assessed up to 24 months]
Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory

Secondary Outcome Measures

Disease Free Survival (DFS) [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]
DFS will be censored for patients who are alive and free of progression at the time of last follow-up. DFS rate will be estimated using the Kaplan-Meier method
Overall Survival (OS) [The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months]
Patients who are still alive when last traced will be censored at the date of last follow-up. OS rate will be estimated using the Kaplan-Meier method

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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