Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in HER2 Positive EsophagoGastric Adenocarcinoma (INTEGA)
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|ClinicalTrials.gov Identifier: NCT03409848|
Recruitment Status : Recruiting
First Posted : January 24, 2018
Last Update Posted : April 9, 2019
The INTEGA study assesses therapy Options for advanced or metastatic esophagogastric Adenocarcinoma in patients overexpressing human epidermal receptor type 2 (HER2 positive patients). Current treatment options in this situation include chemotherapy based palliative treatment in combination withTrastuzumab.
Recent studies have shown that immunotherapy with Nivolumab or Ipilimumab after previous chemotherapy can also improve survival in esophagogastric cancer.
This study assesses the efficacy of two experimental first line treatment strategies: A) Chemo-free immunotherapy with Trastuzumab, Nivolumab and Ipilimumab and B) addition of Nivolumab to the standard regimen (FOLFOX chemotherapy and Trastuzumab).
|Condition or disease||Intervention/treatment||Phase|
|Gastric Cancer Esophageal Cancer Adenocarcinoma Gastric HER2 Positive Gastric Cancer Metastatic Gastric Cancer GastroEsophageal Cancer||Drug: Nivolumab Drug: Ipilimumab||Phase 2|
Gastric cancer is the fifth most common cancer in the world, and the third leading cause of cancer death in both sexes worldwide.
Surgical resection is currently the only curative treatment option for gastric cancer; however, ~50% of patients have metastatic disease at the time of diagnosis and chemotherapy is the mainstay of palliation in this setting.
Trastuzumab, in combination with chemotherapy, significantly improved survival in patients with overexpression of HER2.
In regard of the very limited therapeutic landscape of HER2 positive EGA, compared to breast cancer, further treatment options to relevantly improve the outcome is warranted. The integration of check-point inhibitors (e.g. Nivolumab, Ipilimumab) into the first line setting either within a chemotherapy-free combination arm or within an intensified standard arm of FOLFOX and trastuzumab with nivolumab may be able to improve the current limited survival of median 14 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||97 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in Previously Untreated HER2 Positive Locally Advanced or Metastatic EsophagoGastric Adenocarcinoma|
|Actual Study Start Date :||March 1, 2018|
|Estimated Primary Completion Date :||October 2021|
|Estimated Study Completion Date :||January 2022|
Experimental: A: Chemo-free immunotherapy
Week 1-12 Trastuzumab 6mg/kg d1 every 3 weeks (loading dose 8mg/kg) Nivolumab 1mg/kg i.v. d1 every 3 weeks Ipilimumab 3mg/kg i.v. d1 every 3 weeks Week 13 till EOT (max treatment period 12 months) Trastuzumab 4mg/kg d1 every 2 weeks Nivolumab 240mg i.v. d1 every 2 weeks
Chemo-free immunotherapy with Nivolumab, Ipilimumab, Trastuzumab
Chemo-free immunotherapy with Nivolumab, Ipilimumab, Trastuzumab
Experimental: B: Chemo- / immunotherapy
Trastuzumab 4mg/kg d1 every 2 weeks (loading dose 6mg/kg) Nivolumab 240mg i.v. d1 every 2 weeks mFOLFOX6 every 2 weeks Oxaliplatin at a dose of 85 mg/m2 IV over two hours (day 1) 5-FU 400 mg/m2 IV bolus (day 1) LV at a dose of 400 mg/m2 iv over two hours (day 1) 5-FU at a dose of 2400 mg/m2 IV over 46 hours (day 1-3)
Max Treatment period 12 months
Addition of Nivolumab to Standard therapy (chemotherapy and Trastuzumab)
- Overall Survival [ Time Frame: Milestone at 12 months, max observation period 48 months ]Overall survival including milestone rate at 12 months
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 48 months ]according to Common Terminology Criteria for Adverse Events and to the obtained data on vital signs, clinical parameters and feasibility of the regimen
- Progression Free Survival [ Time Frame: 48 months ]Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)
- Response Rate [ Time Frame: 15 months ]Response Rate (RR) according to RECIST v1.1
- Health related Quality of Life [ Time Frame: 48 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
- Health related Quality of Life [ Time Frame: 48 months ]EORTC STO-22 (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire Gastric Module (STO = stomach) (22 items), comprising five multi-item and four single-item subscales. The multi-item subscales include questions about dysphagia (4 items), dietary restriction (5 items), pain (3 items), upper gastro-esophageal symptoms such as reflux (3 items), and emotional problems such as anxiety (3 items). The single-item subscales include questions related to four gastric cancer-specific symptoms: dry mouth, body image, hair loss, and problems with taste. 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.
- Translational research tumor block [ Time Frame: 48 months ]Tumor-infiltrating lymphocytes (TiL) repertoire determination from tumor
- Translational research blood - immunoprofiling [ Time Frame: Up to 7 weeks ]Liquid biopsy next-generation sequencing (NGS) immunoprofiling (TCRβ & IgH) before treatment initiation and before second cycle to determine response predictive immune signature
- Translational research blood - circulating Tumor cells (CTC) [ Time Frame: 48 months ]CTC will be evaluated for changes in HER2 and PD-L1 status
- Translational research blood - circulating Tumor DNA (ctDNA) [ Time Frame: 48 months ]ctDNA will be evaluated for HER signaling alterations
- Central Imaging Review - ORR [ Time Frame: 48 months ]Retrospective central radiological review of ORR according to modified RECIST
- Central Imaging Review - PFS [ Time Frame: 48 months ]Retrospective central radiological review of PFS according to modified RECIST
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): NCT03409848
|Contact: Katrin Krause||+49 (0)30 8145344 ext 32||Katrin.Krause@aio-studien-ggmbh.de|
|Contact: Wolfgang Hiegl||+49 (0)30 8145344 ext 54||Wolfgang.Hiegl@aio-studien-ggmbh.de|
|Universitätsklinikum Hamburg-Eppendorf Hubertus Wald Tumorzentrum - UCCH II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, KMT mit Sektion Pneumologie)||Recruiting|
|Hamburg, Germany, 20246|
|Contact: Alexander Stein, Dr. firstname.lastname@example.org|
|Principal Investigator:||Alexander Stein, Dr.||Universitätsklinikum Hamburg-Eppendorf Hubertus Wald Tumorzentrum - UCCH II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, KMT mit Sektion Pneumologie)|