NCT03416244

Brief Summary

Cancer - including esophageal squamous cell cancer (ESCC) - is a disease of the elderly but little is known about the biology and progression of cancers in these patients. While most patients receive chemotherapy and/or chemo-radiation as first treatment, no treatment standard for following treatments has been established so far and there is a clear unmet medical need, especially for elderly patients. Hence, this study assesses the efficacy and safety of two experimental immunotherapy regimens (Nivolumab monotherapy or Nivolumab/Ipilimumab combination) in elderly patients with advanced esophageal squamous cell cancer.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
66

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2018

Typical duration for phase_2

Geographic Reach
1 country

1 active site

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

January 24, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 31, 2018

Completed
21 days until next milestone

Study Start

First participant enrolled

February 21, 2018

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 19, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 19, 2021

Completed
Last Updated

September 29, 2022

Status Verified

September 1, 2022

Enrollment Period

3.7 years

First QC Date

January 24, 2018

Last Update Submit

September 28, 2022

Conditions

Esophageal CancerOesophageal CancerOesophageal Cancer MetastaticEsophageal Cancer MetastaticEsophageal Cancers NOSOesophageal Cancer NosGastroEsophageal CancerGastrooesophageal Cancer

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    OS measured from first dose of 2nd line therapy to the date of death

    36 months

Secondary Outcomes (9)

  • Time to QoL deterioration

    36 months

  • Progression free survival

    36 months

  • Objective Response rate

    36 months

  • Duration of response

    36 months

  • Duration of treatment

    36 months

  • +4 more secondary outcomes

Study Arms (2)

A: Nivolumab / Ipilimumab combination treatment

EXPERIMENTAL

Nivolumab 240 mg fixed dose IV every 2 weeks; Additionally, after 7 week safety assessment Ipilimumab 1mg/kg IV every 6 weeks

Drug: NivolumabDrug: Ipilimumab

B. Nivolumab monotherapy

EXPERIMENTAL

Nivolumab 240 mg fixed dose IV every 2 weeks

Drug: Nivolumab

Interventions

NivolumabDRUG

Nivolumab 240 mg IV fixed dose every two weeks

A: Nivolumab / Ipilimumab combination treatmentB. Nivolumab monotherapy
IpilimumabDRUG

Ipilimumab 1mg/kg IV every six weeks (starting in week 7 after safety assessment)

A: Nivolumab / Ipilimumab combination treatment

Eligibility Criteria

Age65 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening Evaluations
  • Age ≥ 65 years at time of study entry
  • Histologically confirmed advanced stage non-resectable esophageal squamous cell carcinoma beyond frontline therapy\*:
  • stage 4 OR
  • stage 3 non-responder to radio-chemotherapy OR
  • any relapse after chemo-radiation OR
  • any relapse after surgery if patient is ineligible or intolerant to standard frontline therapies OR refuses other treatment \* Frontline therapy is defined as chemotherapy (+/-radiotherapy) (e.g. CROSS, FLOT or similar protocols) OR any palliative systemic chemotherapy
  • Geriatric status: SlowGo or GoGo according to G8 and DAFI assessment (G8 \> 14 points or CGA/DAFI 0.2 \< 0.35)
  • At least 1 measurable lesion according to RECIST 1.1
  • Karnofsky performance status ≥ 50
  • Sufficient cardiac functional reserve defined as ejection fraction ≥ 50%
  • Adequate blood count, liver-enzymes, and renal function:
  • neutrophil count \> 1.5 x 10\^6/mL
  • WBC ≥ 3000/μL
  • Platelet count ≥ 100 x 10\^9/L (\>100,000 per mm\^3)
  • +8 more criteria

You may not qualify if:

  • Patients \< 65 years of age
  • Frail patients (DAFI score ≥ 0.35)
  • Esophageal adenocarcinomas, neuroendocrine tumors
  • Prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor \[TNFR\] family), or anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Previous treatment in the present study (does not include screening failure).
  • Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:
  • Major surgery ≤ 28 days prior first dose of study treatment
  • Anticancer treatment during the last 30 days prior to start of Nivolumab monotherapy treatment, including systemic therapy or major surgery \[palliative radiotherapy has to be completed at least 2 weeks prior to start of study treatment\]
  • History of interstitial lung disease
  • Known acute or chronic pancreatitis
  • Known active HBV, HCV or HIV infection
  • Active tuberculosis
  • Any other active infection (viral, fungal or bacterial) requiring systemic therapy
  • History of allogeneic tissue/solid organ transplant
  • Diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Nivolumab monotherapy treatment.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Universitätsmedizin Mannheim, Heidelberg University, II. Medizinische Klinik

Mannheim, 68167, Germany

Location

Related Publications (3)

  • Li M, Meindl-Beinker NM, Maenz M, Betge J, Schulte N, Zhan T, Hofheinz RD, Vogel A, Angermeier S, Bolling C, de Wit M, Jakobs R, Karthaus M, Stocker G, Thuss-Patience P, Leidig T, Bauer H, Ebert MP, Haertel N. Functional status and quality of life in older patients with advanced esophageal squamous cell cancer receiving second-line nivolumab +/- ipilimumab therapy: A post hoc analysis of the phase 2, multicenter RAMONA study. J Geriatr Oncol. 2024 Sep;15(7):101838. doi: 10.1016/j.jgo.2024.101838. Epub 2024 Aug 3.

    PMID: 39097500DERIVED

  • Ebert MP, Meindl-Beinker NM, Gutting T, Maenz M, Betge J, Schulte N, Zhan T, Weidner P, Burgermeister E, Hofheinz R, Vogel A, Angermeier S, Bolling C, de Wit M, Jakobs R, Karthaus M, Stocker G, Thuss-Patience P, Leidig T, Gaiser T, Kather JN, Haertel N. Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial. Lancet Healthy Longev. 2022 Jun;3(6):e417-e427. doi: 10.1016/S2666-7568(22)00116-7. Epub 2022 Jun 9.

    PMID: 36098320DERIVED

  • Meindl-Beinker NM, Betge J, Gutting T, Burgermeister E, Belle S, Zhan T, Schulte N, Maenz M, Ebert MP, Haertel N. A multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for 2nd line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA). BMC Cancer. 2019 Mar 14;19(1):231. doi: 10.1186/s12885-019-5446-2.

    PMID: 30871493DERIVED

Related Links

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

NivolumabIpilimumab

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Matthias Ebert, Prof. Dr.

    Universitätsmedizin Mannheim, Heidelberg University, II. Medizinische Klinik

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 24, 2018

First Posted

January 31, 2018

Study Start

February 21, 2018

Primary Completion

November 19, 2021

Study Completion

November 19, 2021

Last Updated

September 29, 2022

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)