Rectal CancerPhase 2NCT03921684
Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients
A Phase 2 study testing Capecitabine, Radiation therapy and mFOLFOX6 in people with Rectal Cancer, run by Baruch Brenner at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Capecitabine, Radiation therapy and mFOLFOX6
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteIsrael
- Study dates
- 10 Apr 2019to Oct 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer
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.
Patients with cCR will be offered the alternative strategy of WW. Post-study systemic treatment, up to 4 cycles of mFOLFOX6, will be left to the discretion of the treating physician. This will be started 4-8 weeks post-operatively, or immediately after the demonstration of cCR in patients determined to undergo WW.
- Conditions
- Rectal Cancer
- Being tested
- Capecitabine, Radiation therapy, mFOLFOX6, Nivolumab
- Keywords
- Nivolumab, Chemoradiation, mFOLFOX6, rectal cancer, Anti-PD-1 antibody
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Xeloda
Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy
Radiation therapyRadiation
1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine
mFOLFOX6Drug
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
NivolumabDrug
Also called Opdivo
Nivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Treatment | Experimental | All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment Receives: Drug: Capecitabine; Radiation: Radiation therapy; Drug: mFOLFOX6; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response (pCR) rate
pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)
Measured: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
Incidence of Treatment-Emergent Adverse Events (Safety)
Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory
Measured: Time from screening until the end of study drug administration, assessed up to 24 months
modified pathological complete response
We defined a novel primary endpoint, combining pathological complete response (pCR) rate among operated patients and long-term (≥12 months) clinical complete response (cCR) rate for those electing watchful waiting, into a composite endpoint of modified pCR (mpCR) rate.
Measured: Time from start of neoadjuvant treatment until surgical resection in operated patients (pCR) and long-term (≥12 months) clinical complete response (cCR) in unoperated patients, assessed up to 24 months.
Secondary outcomes (2)
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
Measured: 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
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
Measured: The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start10 Apr 2019
- Primary completion28 Oct 2024
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baruch Brenner
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Baruch Brenner, Rabin Medical Center
- Investigators
- Baruch Brenner, Prof, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03921684
- Sponsor's protocol ID
- CA209-8M4
- Status last verified
- Dec 2025
- First submitted
- 14 Apr 2019
- Last updated
- 5 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT03921684
- Acronym / sponsor ID
- CA209-8M4
- Conditions
- Rectal Cancer
- Keywords
- Nivolumab, Chemoradiation, mFOLFOX6, rectal cancer, Anti-PD-1 antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Baruch BrennerUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 10 Apr 2019 (actual)
- Primary completion
- 28 Oct 2024 (actual)
- Study completion
- Oct 2029 (estimated)
- First posted
- 19 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Patients with cCR will be offered the alternative strategy of WW. Post-study systemic treatment, up to 4 cycles of mFOLFOX6, will be left to the discretion of the treating physician. This will be started 4-8 weeks post-operatively, or immediately after the demonstration of cCR in patients determined to undergo WW.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Treatment | Experimental | Drug: Capecitabine, Radiation: Radiation therapy, Drug: mFOLFOX6, Drug: NivolumabAll subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineAlso: XelodaCapecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy | Drug | Neoadjuvant Treatment |
| Radiation therapy1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine | Radiation | Neoadjuvant Treatment |
| mFOLFOX6oxaliplatin 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 | Neoadjuvant Treatment |
| NivolumabAlso: OpdivoNivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6 | Drug | Neoadjuvant Treatment |
Primary outcome
pathological complete response (pCR) rate
Time frame: 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 frame: 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
modified pathological complete response
Time frame: Time from start of neoadjuvant treatment until surgical resection in operated patients (pCR) and long-term (≥12 months) clinical complete response (cCR) in unoperated patients, assessed up to 24 months.
We defined a novel primary endpoint, combining pathological complete response (pCR) rate among operated patients and long-term (≥12 months) clinical complete response (cCR) rate for those electing watchful waiting, into a composite endpoint of modified pCR (mpCR) rate.
2 secondary outcomes
Disease Free Survival (DFS)
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
Overall Survival (OS)
Time frame: The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Baruch Brenner, Prof principal investigator
Rabin Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine, Radiation therapy and mFOLFOX6 in people with Rectal Cancer, run by Baruch Brenner at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological complete response (pCR) rate (time frame: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2026.