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Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

Primary Purpose

Rectal Cancer

Status

Recruiting

Phase

Phase 2

Locations

Israel

Study Type

Interventional

Intervention

Capecitabine

Radiation therapy

mFOLFOX6

Nivolumab

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Nivolumab, Chemoradiation, mFOLFOX6, rectal cancer, Anti-PD-1 antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Rabin Medical Center, Beilinson HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

pathological complete response (pCR) rate

pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)

Incidence of Treatment-Emergent Adverse Events (Safety)

Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT03921684

First Posted

April 14, 2019

Last Updated

April 17, 2019

Sponsor

Baruch Brenner

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT03921684

Brief Title

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

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Recruiting

Study Start Date

April 2019 (Anticipated)

Primary Completion Date

April 2021 (Anticipated)

Study Completion Date

October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Baruch Brenner

Collaborators

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer

Keywords

Nivolumab, Chemoradiation, mFOLFOX6, rectal cancer, Anti-PD-1 antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Other Intervention Name(s)

Xeloda

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Radiation therapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

mFOLFOX6

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

Opdivo

Intervention Description

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

Primary Outcome Measure Information:

Title

pathological complete response (pCR) rate

Description

pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)

Time Frame

Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months

Title

Incidence of Treatment-Emergent Adverse Events (Safety)

Description

Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory

Time Frame

Time from screening until the end of study drug administration, assessed up to 24 months

Secondary Outcome Measure Information:

Title

Disease Free Survival (DFS)

Description

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 Frame

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

Title

Overall Survival (OS)

Description

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

Time Frame

The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Baruch Brenner, Prof

Phone

972-3-9378002

brennerb@clalit.org.il

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Baruch Brenner, Prof

Organizational Affiliation

Rabin Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rabin Medical Center, Beilinson Hospital

City

Petach Tikva

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Baruch Brenner, Prof

First Name & Middle Initial & Last Name & Degree

Baruch Brenner, Prof

12. IPD Sharing Statement

Learn more about this trial

Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

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