Metronomic Oral Vinorelbine Plus Anti-PD-L1/Anti-CTLA4 ImmunothErapy in Patients With Advanced Solid Tumours

NCT03518606 | Completed Phase 1 DMC

• 2 other identifiers: UC-0101/17092017-001857-14
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 9

Brief Summary

This is a phase I/II national, multicentre, multiple cohort, prospective open-label, non-randomised and non-comparative study, to evaluate the safety and activity of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy for the treatment of advanced solid tumours.

Conditions

Advanced Solid Tumours; Breast Cancer; Head and Neck Cancer; Cervix Cancer; Prostate Cancer

Keywords

Advanced solid tumours; Durvalumab; Tremelimumab; Metronomic vinorelbine; High mutational load malignancies; Immunotherapy; Early phase; Combination study

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) and the phase II recommended dose (RP2D)

  Phase I

  9 months

• CBR-24week

  Phase II

  24 months

Study Arms (5)

Breast cancer cohort

EXPERIMENTAL

Patients presenting advanced refractory breast cancer

Drug: Durvalumab + Tremelimumab + metronomic Vinorelbine

Head and neck cohort

EXPERIMENTAL

Patients presenting advanced refractory head and neck cancer

Drug: Durvalumab + Tremelimumab + metronomic Vinorelbine

Cervix cohort

EXPERIMENTAL

Patients presenting advanced refractory cervix cancer

Drug: Durvalumab + Tremelimumab + metronomic Vinorelbine

Prostate cohort

EXPERIMENTAL

Patients presenting advanced refractory prostate cancer

Drug: Durvalumab + Tremelimumab + metronomic Vinorelbine

Miscellaneous cohort

EXPERIMENTAL

Patients presenting advanced refractory solid tumour with high mutational load

Drug: Durvalumab + Tremelimumab + metronomic Vinorelbine

Interventions

Durvalumab + Tremelimumab + metronomic Vinorelbine DRUG

Patient will be treated by metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy

Breast cancer cohort; Cervix cohort; Head and neck cohort; Miscellaneous cohort; Prostate cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have signed a written informed consent form prior to any study specific procedures.
• Histologically confirmed locally advanced or metastatic solid tumours, resistant to conventional therapies, and candidate to experimental therapy by local clinical board, from the following primary tumours:
• Head and neck squamous cell carcinomas,
• Breast cancer,
• Prostate cancer,
• Cervical cancer,
• Miscellaneous primary tumours (except melanoma, non-small cell lung cancer \[NSCLC\], and renal cell cancer) with a high mutational load, as defined by a molecular clinical board after next-generation sequencing (comprehensive cancer gene panel or whole genome/exome sequencing) analysis.
• Patients aged ≥18 years at registration.
• Life expectancy ≥3 months.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Body weight \>30 kg.
• Normal haematological function (ANC ≥1.5 x 10⁹/L; platelets count ≥100 x 10⁹/L; haemoglobin ≥9.0 g/dL).
• Normal hepatic function: total bilirubin ≤1.5 upper limit of normal (ULN) (unless documented Gilbert's syndrome); asparate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 ULN (≤5 ULN in the presence of liver metastases).
• Normal cardiac function: left ventricular ejection fraction (LVEF) ≥50% (any assessment method).

You may not qualify if:

• Other concurrent malignancies, except adequately treated cone-biopsied in situ carcinoma of the cervix, or basal cell or squamous cell carcinoma of the skin. Patients who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥5 years and the risk of recurrence is considered low.
• Active brain metastases, spinal cord compression, or leptomeningeal disease. Patients whose brain metastases have been treated may participate if the brain metastases are stable by imagery (defined as 2 brain images, both obtained after treatment of the brain metastases and at least four weeks apart, and showing no evidence of intracranial progression). In addition, any neurologic symptoms caused by the brain metastases or their treatment must be resolved or stable, without steroidal treatment or with a dose of steroid ≤10 mg/day of prednisone or its equivalent and an anticonvulsants, for at least 14 days prior to the start of treatment.
• Previous treatment with an anti-PD1/PD-L1 including durvalumab or an anti-CTLA-4 therapy including tremelimumab or vinorelbine.
• Patients with known allergy or severe hypersensitivity to any of the study treatments or any of the study treatment excipients.
• History of active primary immunodeficiency.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
• Patients with celiac disease controlled by diet alone.
• History of allogeneic organ transplantation.
• History or evidence of active, non-infectious pneumonitis.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• AstraZeneca: collaborator
• Pierre Fabre Laboratories: collaborator

Study Sites (9)

Institut de Cancérologie de l'Ouest - Site Paul Papin

Angers, France

Location

Centre François Baclesse

Caen, France

Location

Centre Georges-François Leclerc

Dijon, 21079, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• De La Motte Rouge T, Frenel JS, Cropet C, Borcoman E, Hervieu A, Emile G, Augereau P, Charafe E, Legrand F, Dasse E, Goncalves A. Tremelimumab plus durvalumab combined to metronomic oral vinorelbine: Results from the breast cancer cohort of the phase II MOVIE study. Breast. 2025 Oct;83:104549. doi: 10.1016/j.breast.2025.104549. Epub 2025 Aug 5.

  PMID: 40795480 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Head and Neck Neoplasms; Uterine Cervical Neoplasms; Prostatic Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I/II national, multicentre, multiple cohort, prospective open-label, non-randomised and non-comparative study divided in two parts: * Phase I part: dose escalation study of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy, * Phase II part: activity study of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy.

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 8, 2018
• Study Start: June 20, 2018
• Primary Completion: April 1, 2022
• Study Completion: December 19, 2024
• Last Updated: January 15, 2025

Record last verified: 2024-01

Locations

FR (9)