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Potentiation of Cisplatin-based Chemotherapy by Digoxin in Advanced Unresectable Head and Neck Cancer Patients

NCT02906800 · Status: UNKNOWN · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 15

Last updated 2017-10-19

No results posted yet for this study

Summary

Introduction: Patients with primary unresectable advanced head and neck squamous cell carcinomas (HNSCC) have a poor prognosis with a median survival of 22 months (Hauswald H Radiat Oncol 2011). They are usually treated with induction chemotherapy followed by radiochemotherapy or platinum-based concomitant radiochemotherapy. Most patients achieve an objective clinical response contrasting with a high rate of local recurrence and distant metastases in the year following radiochemotherapy (Argiris A Ann Oncol 2011). Improvement of the efficacy of chemotherapy remains therefore a major clinical goal for this group of patients. During the past years, the investigators demonstrated that some conventional chemotherapeutics (anthracycline, oxaliplatin…) induce a type of "immunogenic" cell death (ICD) characterized by the exposure of calreticulin on the tumor cell surface, the secretion of ATP and the release of high-mobility group box 1 (HMGB1) resulting in activation of tumor immunity (Galluzzi L Nat Rev Drug Discov 2012). The investigators recently showed that the Na/K-ATPase inhibitor, digoxin, favors ICD, when combined with cisplatin, a drug known not to induce ICD. In preclinical models, a synergy between cisplatin and digoxin which led to a significant therapeutic improvement (Menger L Sci Transl Med 2012) has been observed. This effect seems to be mediated by the immune system as the combined therapy induced intratumor T cell infiltration producing cytokines (Menger L Sci Transl Med 2012).

Hypothesis: Based on our preclinical data, the hypothesis is that adding digoxin to the conventional cisplatin based induction chemotherapy regimen in unresectable advanced HNSCC will increase the efficacy of this therapy via the induction of anti-tumor immunity.

Objectives:

Main: the primary objective is to assess the clinical and biological safety of the combination of digoxin to cisplatin-based chemotherapy.

Secondary: The secondary objectives are to investigate biological markers of efficacy by analyzing the recruitment of functional T cells in tumour biopsies after treatment with the combination of digoxin and chemotherapy.

Conditions

Interventions

DRUG

Digoxin

The digoxin dose will be adjusted to achieve a plasma concentration of 0.6-1.2 ng/ml according to current recommendations in heart failure patients (doses adapted to renal function, comorbidities, concomitant medications, age, and plasma concentration). The risk related to digoxin treatment will be minimized in our study since the duration of exposure to digoxin will be limited to 9 days every 3 weeks for 3 cycles (total duration of treatment 27 days).

Sponsors & Collaborators

  • Cancer Research and Personalized Medicine (Carpem)

    collaborator UNKNOWN

  • Laboratoire d'excellence en immuno-oncologie (Labex)

    collaborator UNKNOWN

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Principal Investigators

  • Stephane HANS, MD, PH · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
19 Years
Max Age
69 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-01-31
Primary Completion
2019-05-31
Completion
2019-05-31

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02906800 on ClinicalTrials.gov