Early Palliative Care in Patients With Metastatic Upper Gastrointestinal Cancers Treated With First-line Chemotherapy

NCT ID: NCT02853474

Last Updated: 2023-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2022-12-31

Brief Summary

This prospective, randomized, open-label and multicenter phase III study is aimed to estimate the survival benefit of Early Palliative Care (EPC) combined with standard oncology care including first-line chemotherapy (experimental arm) over standard oncology care only (standard arm), in patients with metastatic upper gastrointestinal cancers (gastric cancer, pancreatic cancer, biliary tract cancers).

Detailed Description

Medical oncology is aimed to increase patient's survival, even at metastatic stages, in addition to disease-related and treatment-related symptoms. However, providing palliative care (PC) which includes symptoms management, nutritional support, psychosocial support, as well as assistance on end-of-life preferences, may be as important as survival issues to improve quality of life in such setting. In France, PC has been traditionally offered late, at end-life stage, although the World Health Organization recommends providing PC as earlier as possible in the course of the disease, in order to increase quality of life.

Decades ago, PC services were initiated in France in order to provide a medical alternative to the use of questionable medical practices regarding the end of life period: abandonment, euthanasia, and inappropriate aggressive therapy. According to the French society of palliative care, PC is an approach aimed to provide active care, in a holistic approach, to the person with a serious, progressive or terminal illness. The objective of PC is to relieve pain and other distressing symptoms, but also to take into account the psychological, social and spiritual suffering. PC offers an interdisciplinary support system to help patients and their relatives. As mentioned previously, PC has been in France (but also in the US) usually offered late, at end-life stage. Actually, PC access became a Right guaranteed by the Law, for patients and their families in 1999. This context should explain why even nowadays, PC often means " end of life " not only for the lay-man for the general public but also for caregivers, and some doctors.

The last World Health Organization (WHO) recommendations are far less restrictive than the 1996 French recommendations, as it is stated that PC should be offered as earlier as possible in the course of the disease, in order to increase quality of life, and to positively influence the course of illness. The World Health Organization recommendations add that PC is applicable early in the course of illness, in conjunction with other therapies that are intended to prolong life, such as chemotherapy or radiation therapy, and includes those investigations needed to better understand and manage distressing clinical complications.

In a recent randomized study, 151 patients with newly diagnosed metastatic non-small-cell lung cancer were randomized to receive either early PC (EPC) combined with standard oncologic care or standard oncologic care alone. It was hypothesized that patients, who received EPC, compared with patients who received standard oncologic care only, would have a better quality of life (primary endpoint). The first visit with the PC service set up within the first 12 weeks, and the median number of visits in the EPC group was 4. In this study, the authors referred to the recommendations of the National Consensus Project for Quality Palliative Care. Among patients with metastatic non-small-cell lung cancer, EPC led to significant improvements in quality of life. In addition, EPC led to significant improvements in mood, as well as in overall survival (median survival, 11.6 vs. 8.9 months; HR=0.60, p = 0.02)), despite less aggressive end-of-life care.

Following the publication of this American study, the American Society of Clinical Oncology recommends nowadays that "combined standard oncology care and PC should be considered earlier in the course of the illness for any patient with metastatic cancer….". However, it is clear that a gap exists (not only in France) between this recommendation and the current practice. In addition, there is no consensus on how early PC should be integrated in oncologic services, even though an underpowered small randomized trial reported recently an insignificant better survival favoring early versus delayed (3 months later) initiation of PC.

The results of the study described above, although formally restricted to the field of metastatic non-small-cell lung cancers, have modified the perception of many oncologists about the objectives of PC. However, additional clinical studies should be done before considering EPC as an additional survival input in other advanced malignancies.

The median survival of metastatic upper gastrointestinal (GI) cancers such as pancreatic cancers, gastric cancers, and biliary tract cancers did not exceed 10-11 months, which is as poor as reported with metastatic lung cancers. Standard of care in the metastatic setting in upper GI cancers are described in ad hoc French guidelines, i.e.: "Thésaurus National de Cancérologie Digestive". Briefly, standard of care in metastatic pancreatic cancer in the first-line setting lies on the combination of fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX regimen) for patients without any cholestasis and in good performance status, and on gemcitabine monotherapy. In metastatic biliary tract cancers, standard of care lies on gemcitabine-based regimen (gemcitabine monotherapy, gemcitabine plus cisplatin, or gemcitabine plus fluorouracil). Besides HER2 positive metastatic gastric/gastrooesophageal patients who present with much better prognosis, and should be treated with trastuzumab-based regimen, most of patients with metastatic gastric/gastrooesophageal HER2 negative patients (IHC + or IHC ++ with negative fish/sish) have poor prognosis, with similar survival rates than patients with other upper GI malignancies. In that setting, several regimens may be offered to patients, such as the following: Folfox, EOX/ECX, Folfiri, LV5FU2-cisplatin, Capecitabine-platinum salt or docetaxel-based regimen ...). Several experimental treatments (antiangiogenics, met inhibitors, modulators of immune check points, etc...) are currently tested in metastatic gastric/gastrooesophageal cancers, but these treatments are restricted to patients in good health condition who accept to participate to clinical trials, and none of these trials have yet produced meaningful survival benefit in the first-line setting.

To summarize, therapeutic advances in the setting of metastatic upper GI cancers are infrequent, and often modest. Providing an extra survival benefit for these patients with EPC, may contribute to deeply modify the practice of care of oncology in France.

Conditions

Gastric Cancer; Pancreas Cancer; Bile Duct Cancer; Gastroesophageal Cancer; Esophageal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Arm A: Chemotherapy (CT) alone

The medical oncologists (or gastro enterologist physician) are in charge of the patient for CT administration, and for the management of symptoms related to the disease and/or the treatment, in accordance with professional practices. If needed (any time), a PC (Palliative consultation) visit could be performed.

Interventions are :

• EORTC-QLQ-C30 questionnaire for the assessment of quality of life
• HADS score for anxiety and depression assessment

Group Type: SHAM_COMPARATOR

EORTC-QLQ-C30 questionnaire

Intervention Type: OTHER

The Quality of Life is assessed with the QLQ-C30 questionnaire at baseline, 12 and 24 weeks after inclusion, as well as every 8 weeks thereafter.

HADS score

Intervention Type: OTHER

The depression is assessed with the HADS scale (Hospital Anxiety and Depression Scale) at baseline, and then 12 and 24 weeks after inclusion.

Arm B: CT + Early Palliative care(EPC)

Standard oncology care as for arm A plus early PC visits.

Interventions are :

• EORTC-QLQ-C30 questionnaire for the assessment of quality of life
• HADS score for anxiety and depression assessment
• Early palliative care visits

Group Type: EXPERIMENTAL

Early Palliative Care visit

Intervention Type: BEHAVIORAL

A PC visit is a visit done by a PC physician. Any kind of visits done by other professionals IS NOT a PC visit.

Five PC visits are scheduled in this arm.

EORTC-QLQ-C30 questionnaire

Intervention Type: OTHER

The Quality of Life is assessed with the QLQ-C30 questionnaire at baseline, 12 and 24 weeks after inclusion, as well as every 8 weeks thereafter.

HADS score

Intervention Type: OTHER

The depression is assessed with the HADS scale (Hospital Anxiety and Depression Scale) at baseline, and then 12 and 24 weeks after inclusion.

Interventions

Early Palliative Care visit

A PC visit is a visit done by a PC physician. Any kind of visits done by other professionals IS NOT a PC visit.

Five PC visits are scheduled in this arm.

Intervention Type: BEHAVIORAL

EORTC-QLQ-C30 questionnaire

The Quality of Life is assessed with the QLQ-C30 questionnaire at baseline, 12 and 24 weeks after inclusion, as well as every 8 weeks thereafter.

Intervention Type: OTHER

HADS score

The depression is assessed with the HADS scale (Hospital Anxiety and Depression Scale) at baseline, and then 12 and 24 weeks after inclusion.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients with an upper gastrointestinal metastatic cancer: pancreatic, biliary tract, esophageal or gastric (including junctional Siewert 2 and 3 cancers) cancers.

NB: gastrooesophageal junctional cancers with dysphagia and/or gastric/gastrooesophageal cancers with unknown or positive HER2 status are not eligible.

• Patients planed to be treated with first-line chemotherapy for metastatic disease.
• Age ≥ 18 years
• Life expectancy ≥ 1 month
• Performance status (OMS) ≤ 2
• Good understanding of French language
• Signed and dated informed consent
• Patients covered by government health insurance

Exclusion Criteria

• Locally advanced cancer
• Junctional Siewert 1 gastrooesophageal cancer
• Gastric or junctional gastrooesophageal cancer with dysphagia (Atkinson>2)
• Gastric or junctional gastrooesophageal cancer with unknown or positive HER2 status (IHC: +++ or IHC ++ and FISH/SISH +)
• Compression of the biliary tract requiring a bypass

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ligue contre le cancer, France

OTHER

Sponsor Role: collaborator

Région Nord-Pas de Calais, France

OTHER

Sponsor Role: collaborator

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arlette Da Silva, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret

Antoine Adenis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret

Locations

Institut de cancérologie de l'Ouest-site PAUL

Angers, , France

CH de Béthune

Beuvry, , France

Centre Hospitalier Boulogne sur Mer

Boulogne-sur-Mer, , France

Centre François Baclesse, Caen

Caen, , France

Centre Georges Francois Leclerc de DIJON

Dijon, , France

Centre Oscar Lambret

Lille, , France

Hôpital Saint Vincent de Paul

Lille, , France

CHRU, Hôpital Claude HURIEZ

Lille, , France

Centre Léon Bérard de LYON

Lyon, , France

Institut Paoli-Calmettes de MARSEILLE

Marseille, , France

Institut du Cancer de Montpellier

Montpellier, , France

Institut de cancérologie de Lorraine, Nancy

Nancy, , France

Institut de cancérologie de l'Ouest, Nantes

Nantes, , France

Centre Antoine LACASSAGNE DE NICE

Nice, , France

Institut Curie, site de Saint Cloud, Hopital

Saint-Cloud, , France

CHU de Nantes, CHU - hôpital Nord Laennec,

Saint-Herblain, , France

Centre Hospitalier Universitaire de STRASBOURG

Strasbourg, , France

Centre Paul Strauss, Strasbourg

Strasbourg, , France

Centre Hospitalier de Tourcoing

Tourcoing, , France

Centre Hospitalier de Valenciennes

Valenciennes, , France

Countries

France

References

Adenis A, Da Silva A, Ben Abdelghani M, Bourgeois V, Bogart E, Turpin A, Evin A, Proux A, Galais MP, Jaraudias C, Quintin J, Bouquet G, Samalin E, Bremaud N, Javed S, Henry A, Kurtz JE, Cornuault-Foubert D, Vandamme H, Lucchi E, Pannier D, Belletier C, Paul M, Touzet L, Penel N, Chvetzoff G, Le Deley MC. Early palliative care and overall survival in patients with metastatic upper gastrointestinal cancers (EPIC): a multicentre, open-label, randomised controlled phase 3 trial. EClinicalMedicine. 2024 Jun 28;74:102470. doi: 10.1016/j.eclinm.2024.102470. eCollection 2024 Aug.

Reference Type: DERIVED

PMID: 39526177 (View on PubMed)

Hutt E, Da Silva A, Bogart E, Le Lay-Diomande S, Pannier D, Delaine-Clisant S, Le Deley MC, Adenis A. Impact of early palliative care on overall survival of patients with metastatic upper gastrointestinal cancers treated with first-line chemotherapy: a randomised phase III trial. BMJ Open. 2018 Jan 23;8(1):e015904. doi: 10.1136/bmjopen-2017-015904.

Reference Type: DERIVED

PMID: 29362244 (View on PubMed)

Other Identifiers

2015-A01943-46

Identifier Type: OTHER

Identifier Source: secondary_id

EPIC-1511

Identifier Type: -

Identifier Source: org_study_id