A Trial of Durvalumab and Tremelimumab in Combination With SBRT in Patients With Metastatic Cancer

NCT03212469 | Completed Phase 1

• 2 other identifiers: 2024-514920-18-002016/2454
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The study is an open label, multicentric, Phase I/II trial aiming to evaluate the safety, the clinical activity and abscopal anti-tumor effects of a therapeutic strategy associating Durvalumab in conjunction with SBRT or Durvalumab + Tremelimumab in conjunction with SBRT in patients with metastatic squamous cell carcinoma of head and neck, lung, or esophagus.

Conditions

Head and Neck Squamous Cell Carcinoma; Lung Cancer; Oesophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Event possibly related to study drugs and fulfills any one of the following criteria using CTCAE Version 4.03

  Approximately 8 weeks

Study Arms (3)

Patients with head and neck squamous cell carcinoma

EXPERIMENTAL

Drug: Durvalumab; Drug: Tremelimumab; Radiation: SBRT

Patients lung cancer

EXPERIMENTAL

Drug: Durvalumab; Drug: Tremelimumab; Radiation: SBRT

Patients with oesophagus cancer

EXPERIMENTAL

Drug: Durvalumab; Drug: Tremelimumab; Radiation: SBRT

Interventions

Durvalumab DRUG

Preliminary steps : Safety Runs Safety run of the dual combination Durvalumab as single agent at the selected dose of 1500mg, every 4 weeks (Q4W) from C1D1 up to 13 doses Safety run of the triple combination: Durvalumab at 1500mg every 4 weeks (Q4W) from C1D1 up to 13 doses, Efficacy step * Durvalumab Q4W + Tremelimumab Q4W for up to 4 doses at the DL defined in safety runs, in conjunction with * SBRT at C1D15, then * Durvalumab Q4W alone for up to 9 additional doses

Patients lung cancer; Patients with head and neck squamous cell carcinoma; Patients with oesophagus cancer

Tremelimumab DRUG

Preliminary steps : Safety Runs Safety run of the triple combination: Tremelimumab at 75mg/Q4W for up to 4 doses Efficacy step * Durvalumab Q4W + Tremelimumab Q4W for up to 4 doses at the DL defined in safety runs, in conjunction with * SBRT at C1D15, then * Durvalumab Q4W alone for up to 9 additional doses

Patients lung cancer; Patients with head and neck squamous cell carcinoma; Patients with oesophagus cancer

SBRT RADIATION

Preliminary steps : Safety Runs Safety run of the dual combination: SBRT at C1D15. Safety run of the triple combination: SBRT at C1D15. Efficacy step * Durvalumab Q4W + Tremelimumab Q4W for up to 4 doses at the DL defined in safety runs, in conjunction with * SBRT at C1D15, then * Durvalumab Q4W alone for up to 9 additional doses

Patients lung cancer; Patients with head and neck squamous cell carcinoma; Patients with oesophagus cancer

Eligibility Criteria

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

You may qualify if:

• I1. Male or Female patients ≥18 years of age or older.
• I2. Histologically or cytologically proven metastatic squamous cell carcinoma (from head and neck, oesophagus, lung, cervix, vagina, vulva or anus) with the following features:
• Previously treated with at least one prior regimen (chemotherapy, signal transduction inhibitors or radiotherapy)
• To be treated with radiotherapy at primary tumor site or metastatic site or menacing metastatic site.
• The sites of metastases allowed are: soft tissue, peripheral lung, and liver.
• Patients with brain and bone metastasis to be treated with radiotherapy are not allowed. Patients with asymptomatic brain metastasis can be included.
• The total tumor volume to be irradiated must not exceed 400 cc.
• I3. At least one tumor lesion must be accessible to radiation therapy and at least another tumor site can be spared from radiation therapy (unirradiated site).
• I4. At least one unirradiated and one irradiated tumor site must be accessible to tumor biopsy.
• I5. Known availability of an archived block
• I6. The irradiated and unirradiated tumor sites must be measurable as per RECIST 1.1
• I7. Patients must have no history of previous radiation therapy within the body area to be irradiated.
• I8. Minimal wash-out periods from previous treatments to C1D1 must be
• Any investigational agent \> 4 weeks
• Bevacizumab \> 6 weeks

You may not qualify if:

• E1. Any situation where the irradiation of the target site would imply reirradiation of a formerly irradiated tumor site.
• E2. Patients with any concurrent severe and/or uncontrolled disease which could compromise participation in the study including:
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Active or prior documented autoimmune disease within the past 2 years. Of note, patient with vitiligo, Grave's disease or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Patients with type 1 diabetes or hypothyroidism stable under treatment or not requiring systemic treatment are eligible.
• Active or prior documented inflammatory bowel disease (eg Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency
• Severe chronic or acute infection such as chronic HBV, HCV and HIV1, 2 infection, active tuberculosis infection
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active non-infectious pneumonitis
• History of allogenic organ transplant
• Uncontrolled diabetes,
• Prior history of active bleeding diathesis or patients taking an oral vitamin K antagonist (except low-dose Coumadin (warfarin sodium))
• Symptomatic congestive heart failure,
• Uncontrolled hypertension,
• Unstable angina pectoris
• Cardiac arrhythmia

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Lung Neoplasms; Esophageal Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Eric DEUTSCH, MD, PhD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

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: The study is an open label, multicentric, Phase I/II trial

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: July 11, 2017
• Study Start: June 20, 2017
• Primary Completion: February 24, 2025
• Study Completion: February 24, 2025
• Last Updated: May 8, 2025

Record last verified: 2025-05

Locations

FR (1)