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)
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|ClinicalTrials.gov Identifier: NCT03416244|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2018
Last Update Posted : October 5, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer Oesophageal Cancer Oesophageal Cancer Metastatic Esophageal Cancer Metastatic Esophageal Cancers NOS Oesophageal Cancer Nos GastroEsophageal Cancer Gastrooesophageal Cancer||Drug: Nivolumab Drug: Ipilimumab||Phase 2|
Cancer - including esophageal squamous cell cancer (ESCC) - is a disease of the elderly, more than 60% of all tumors arise in patients with the age of 65 years or older. In contrast, little is known about the biology and progression of cancers in these patients, since most clinical trials enroll patients with age limits of 70 or 75 years.
While most patients undergo chemotherapy and/or chemo-radiation in first-line, the role of second-line therapy is less well understood. No treatment standard has been established so far and there is a clear unmet medical need. This is particularly true for geriatric patients for whom palliative systemic therapies are especially challenging.
Hence, the primary objective of this trial is to demonstrate a significant survival benefit of two experimental immunotherapy regimens (Nivolumab monotherapy or Nivolumab/Ipilimumab combination) in elderly patients with advanced esophageal squamous cell cancer compared to historical data of standard chemotherapy regimens.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||February 21, 2018|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||August 2021|
Experimental: A: Nivolumab / Ipilimumab combination treatment
Nivolumab 240 mg fixed dose IV every 2 weeks; Additionally, after 7 week safety assessment Ipilimumab 1mg/kg IV every 6 weeks
Nivolumab 240 mg IV fixed dose every two weeks
Ipilimumab 1mg/kg IV every six weeks (starting in week 7 after safety assessment)
Experimental: B. Nivolumab monotherapy
Nivolumab 240 mg fixed dose IV every 2 weeks
Nivolumab 240 mg IV fixed dose every two weeks
- Overall survival [ Time Frame: 36 months ]OS measured from first dose of 2nd line therapy to the date of death
- Time to QoL deterioration [ Time Frame: 36 months ]Time to QoL deterioration defined as a loss of ≥ 10 points in the EORTC QLQ-C30 compared to base-line
- Progression free survival [ Time Frame: 36 months ]Time from first dosing date to the date of the first documented tumor progression
- Objective Response rate [ Time Frame: 36 months ]Proportion of treated subjects with response from baseline
- Duration of response [ Time Frame: 36 months ]Time from first confirmed response to the date of the documented progressive disease or death
- Duration of treatment [ Time Frame: 36 months ]Time from date of first dose of Nivolumab monotherapy until permanent discontinuation of either NIVO mono therapy or NIVO/IPI combination treatment.
- Cumulative dose intensity [ Time Frame: 36 months ]Cumulative dose for each IMP
- Quality of Life C30 [ Time Frame: 36 months ]
EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire (30 items) Version 3.0. The QLQ-C30 is composed of multi-item scales and single-item measures, including five functional scales, three symptom scales, a global health status / QoL scale, and six single items.
All of the scales and single-item measures have a score range from 0 to 100. A high score shows a high response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems
- Quality of Life ELD14 [ Time Frame: 36 months ]EORTC QLQ-ELD14 (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire Module for elderly Cancer patients (14 items), comprising five multi-item and two single-item subscales. The multi-item subscales include questions about mobility (3 items), worries about others (2 items), worries (3 items), maintaining purpose (2 items), and burden of illness (2 items). The single-item subscales include questions related to joint stiffness and Family support. Items are assessed on a 4-level numerical scale with 1= "not at all", 2= "a little", 3= "quite a bit", and 4= "very much". Scores are linearly converted and summated into a scaled score from 0 to 100, with a higher score representing a worse QOL or better QOL for purpose and family support.
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: 36 months ]AE/SAE evaluation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03416244
|Universitätsmedizin Mannheim, Heidelberg University, II. Medizinische Klinik|
|Mannheim, Germany, 68167|
|Principal Investigator:||Matthias Ebert, Prof. Dr.||Universitätsmedizin Mannheim, Heidelberg University, II. Medizinische Klinik|