Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors

NCT03509012 | Completed Phase 1 FDA Drug

• 2 other identifiers: D933BC000012017-002242-77
• Study Type: interventional
• Target: 105
• Locations: 5 countries
• Sites: 16

Brief Summary

This is an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors

Conditions

Carcinoma, Squamous Cell of Head and Neck; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Keywords

Durvalumab; Chemotherapy; Radiotherapy; HNSCC; NSCLC; SCLC; locally-advanced; limited stage; first line

Outcome Measures

Primary Outcomes (2)

• Number of subjects with Dose Limiting Toxicities (DLTs)

  From first dose of durvalumab until 28 days after completion of radiation therapy

• Number of subjects with Adverse Events (AEs)

  From first dose of durvalumab up to 90 days after the last dose of study treatment

Secondary Outcomes (7)

• Progression-free survival (PFS)

  From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years.

• Overall Survival (OS)

  From first dose until death due to any cause through study completion, up to 4 years

• Objective response rate (ORR)

  From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.

• Best objective response (BoR)

  From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.

• Duration of response (DoR)

  From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.

Study Arms (8)

HNSCC Arm 1

EXPERIMENTAL

Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)

Drug: Durvalumab; Drug: Cisplatin (dose level 4); Radiation: External beam radiation (dose level 1)

NSCLC Arm 1

EXPERIMENTAL

Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)

Drug: Durvalumab; Drug: Etoposide (dose level 1); Radiation: External beam radiation (dose level 2); Drug: Cisplatin (dose level 1)

NSCLC Arm 2

EXPERIMENTAL

Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)

Drug: Durvalumab; Drug: Carboplatin (dose level 1); Drug: Paclitaxel; Radiation: External beam radiation (dose level 2)

NSCLC Arm 3

EXPERIMENTAL

Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed

Drug: Durvalumab; Drug: Carboplatin (dose level 2); Drug: Pemetrexed; Radiation: External beam radiation (dose level 2); Drug: Cisplatin (dose level 2)

SCLC Arm 1

EXPERIMENTAL

Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin

Drug: Durvalumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (standard)

SCLC Arm 2

EXPERIMENTAL

Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin

Drug: Durvalumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (hyperfractionated)

SCLC Arm 3

EXPERIMENTAL

Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.

Drug: Durvalumab; Drug: Tremelimumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (standard)

SCLC Arm 4

EXPERIMENTAL

Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.

Drug: Durvalumab; Drug: Tremelimumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (hyperfractionated)

Interventions

Durvalumab DRUG

IV (intravenous)

Also known as: MEDI4736

HNSCC Arm 1; NSCLC Arm 1; NSCLC Arm 2; NSCLC Arm 3; SCLC Arm 1; SCLC Arm 2; SCLC Arm 3; SCLC Arm 4

Tremelimumab DRUG

IV

SCLC Arm 3; SCLC Arm 4

Cisplatin (dose level 4) DRUG

IV

HNSCC Arm 1

Cisplatin (dose level 3) DRUG

IV

SCLC Arm 1; SCLC Arm 2; SCLC Arm 3; SCLC Arm 4

Carboplatin (dose level 1) DRUG

IV

NSCLC Arm 2

Carboplatin (dose level 2) DRUG

IV

NSCLC Arm 3; SCLC Arm 1; SCLC Arm 2; SCLC Arm 3; SCLC Arm 4

Etoposide (dose level 1) DRUG

IV

NSCLC Arm 1

Etoposide (dose level 2) DRUG

IV

SCLC Arm 1; SCLC Arm 2; SCLC Arm 3; SCLC Arm 4

Paclitaxel DRUG

IV

NSCLC Arm 2

Pemetrexed DRUG

IV

NSCLC Arm 3

External beam radiation (dose level 1) RADIATION

radiation therapy

HNSCC Arm 1

External beam radiation (dose level 2) RADIATION

radiation therapy

NSCLC Arm 1; NSCLC Arm 2; NSCLC Arm 3

External beam radiation (hyperfractionated) RADIATION

radiation therapy

SCLC Arm 2; SCLC Arm 4

Cisplatin (dose level 1) DRUG

IV

NSCLC Arm 1

Cisplatin (dose level 2) DRUG

IV

NSCLC Arm 3

External beam radiation (standard) RADIATION

radiation therapy

SCLC Arm 1; SCLC Arm 3

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• World Health Organization (WHO)/ECOG performance status of 0 or 1
• Body weight \>30 kg at enrollment and treatment assignment
• At least 1 measurable lesion, not previously irradiated
• No prior exposure to immune-mediated therapy (including therapeutic anticancer vaccines)
• For patients with oropharyngeal HNSCC HPV status has to be known

You may not qualify if:

• Patients with simultaneous primary malignancies or bilateral tumors
• Active or prior documented autoimmune or inflammatory disorders
• Brain metastases or spinal cord compression
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies)
• Has a paraneoplastic syndrome (PNS) of autoimmune nature
• HNSCC cohort: Head and neck cancer that does not include unresectable, locally advanced cancer of oral cavity, larynx, oropharynx or hypopharynx. HNSCC of unknown primary are also excluded
• NSCLC and SCLC cohort: Mixed SCLC and NSCLC histology
• SCLC cohort: Extensive-stage SCLC

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (16)

Research Site

Tucson, Arizona, 85719, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Houston, Texas, 77090, United States

Location

Research Site

Kōtoku, 135-8550, Japan

Location

Research Site

Sunto-gun, 411-8777, Japan

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Badalona, 08916, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Málaga, 29010, Spain

Location

Research Site

Taichung, 40705, Taiwan

Location

Research Site

Taipei, 10002, Taiwan

Location

Research Site

Taipei, 112, Taiwan

Location

Research Site

Taoyuan, 333, Taiwan

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

durvalumab; tremelimumab; Cisplatin; Carboplatin; Etoposide; Paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Design

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

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: April 26, 2018
• Study Start: May 2, 2018
• Primary Completion: December 31, 2020
• Study Completion: January 8, 2025
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (3); ES (3); TW (4); JP (2); KR (4)