Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03921684
• Other study ID #: CA209-8M4
• Status: Recruiting
• Phase: Phase 2
• Start date: April 2019
• Est. completion date: October 2025

Study information

• Verified date: April 2019
• Source: Rabin Medical Center
• Contact: Baruch Brenner, Prof
• Phone: 972-3-9378002
• Email: brennerb[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: October 2025
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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

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

Locations

Country	Name	City	State
Israel	Rabin Medical Center, Beilinson Hospital	Petach Tikva

Sponsors (2)

Lead Sponsor	Collaborator
Baruch Brenner	Bristol-Myers Squibb

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pathological complete response (pCR) rate	pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)	Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
Primary	Incidence of Treatment-Emergent Adverse Events (Safety)	Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory	Time from screening until the end of study drug administration, assessed up to 24 months
Secondary	Disease Free Survival (DFS)	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	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
Secondary	Overall Survival (OS)	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	The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months