NCT04124601

Brief Summary

This prospective randomized, open-label, multicenter, phase II clinical trial investigates the safety and tolerability of standard neoadjuvant chemoradiotherapy (CRT) with sequential ipilimumab and nivolumab in rectal cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jun 2020

Typical duration for phase_2

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 10, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 11, 2019

Completed
8 months until next milestone

Study Start

First participant enrolled

June 1, 2020

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2024

Completed
Last Updated

April 23, 2024

Status Verified

April 1, 2024

Enrollment Period

3.8 years

First QC Date

October 10, 2019

Last Update Submit

April 20, 2024

Conditions

Keywords

IpilimumabNivolumabChemoradiotherapyRectal cancer

Outcome Measures

Primary Outcomes (1)

  • Incidence of treatment-emergent adverse events (safety and tolerability)

    Incidence of treatment-emergent adverse events will be assessed according to the latest "Clavien- Dindo Classification of surgical complications" and Common Terminology Criteria of Adverse Events (CTCAE).

    20 weeks

Secondary Outcomes (2)

  • Radiographic therapy response between pre-and post-neoadjuvant treatment

    20 weeks

  • Pathologic therapy response to neoadjuvant treatment

    20 weeks

Study Arms (2)

Neoadjuvant Chemoradiotherapy

OTHER

Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days)

Radiation: Chemoradiotherapy

Neoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab

EXPERIMENTAL

Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days) with sequential Ipilimumab (1 mg/kg IV on day 7) and Nivolumab (3 mg/kg IV on day 14, 28 and 42)

Radiation: ChemoradiotherapyDrug: IpilimumabDrug: Nivolumab

Interventions

Capecitabine tablet with fractionated radiotherapy

Also known as: Radiochemotherapy, Chemoradiation
Neoadjuvant ChemoradiotherapyNeoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab

Infusion

Also known as: Yervoy®
Neoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab

Infusion

Also known as: Opdivo®
Neoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age and older
  • All sexes
  • Histologically confirmed carcinoma of the rectum
  • Suitable for local therapy with curative intent
  • Medical need for a standard neoadjuvant CRT
  • Suitable to withstand a course of standard neoadjuvant CRT
  • Written informed consent form (ICF) for participation in the study
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

  • Metastatic disease that is considered incurable by local therapies
  • Previous surgery of the tumor other than biopsy
  • Pregnancy, breastfeeding or expectancy to conceive
  • Disagreement of participants with reproductive potential to use contraception throughout the study period and for up to 180 days after the last dose of study therapy
  • Prior therapy with anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 or any other agent directed against co-inhibitory T cell receptors or has previously participated in clinical studies with immunotherapy
  • Any contraindication according to the official medical information of Ipilimumab or Nivolumab
  • Live vaccine within 30 days prior to the first dose of study therapy
  • Hepatitis B or C
  • Human immunodeficiency virus (HIV)
  • Immunodeficiency
  • Allogeneic tissue or solid organ transplantation
  • Autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, steroids or immunosuppressive drugs
  • Systemic steroids or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Active non-infectious pneumonitis
  • Active infection requiring systemic therapy
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

State Hospital Wiener Neustadt

Wiener Neustadt, Lower Austria, Austria

Location

Congregational Hospital Linz - Sisters of Mercy

Linz, 4010, Austria

Location

Hospital of St. John of God

Vienna, 1020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Hospital North - Clinic Floridsdorf

Vienna, 1210, Austria

Location

Related Publications (1)

  • Laengle J, Kuehrer I, Kulu A, Kabiljo J, Ammon D, Zirnbauer R, Stift A, Herbst F, Dauser B, Monschein M, Razek P, Haegele S, Biebl M, Geinitz H, Hulla W, Kalinina P, Mullauer L, Widder J, Bittermann C, Pils D, Tamandl D, Laengle F, Schmid R, Bergmann M. Dual Immune Checkpoint Inhibition Plus Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2527769. doi: 10.1001/jamanetworkopen.2025.27769.

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

ChemoradiotherapyIpilimumabNivolumab

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality TherapyTherapeuticsDrug TherapyRadiotherapyAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Michael Bergmann, MD

    Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Sponsor-Investigator

Study Record Dates

First Submitted

October 10, 2019

First Posted

October 11, 2019

Study Start

June 1, 2020

Primary Completion

March 15, 2024

Study Completion

March 15, 2024

Last Updated

April 23, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations