Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors

Phase 1

Active, not recruiting

• Conditions: Carcinoma, Squamous Cell of Head and Neck; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma
• Interventions: Drug: Durvalumab; Drug: Cisplatin (dose level 4); Drug: Etoposide (dose level 1); Drug: Carboplatin (dose level 1); Drug: Cisplatin (dose level 3); Drug: Tremelimumab; Drug: Carboplatin (dose level 2); Radiation: External beam radiation (dose level 1); Drug: Pemetrexed; Drug: Paclitaxel; Drug: Etoposide (dose level 2); Drug: Cisplatin (dose level 1); Radiation: External beam radiation (dose level 2); Drug: Cisplatin (dose level 2); Radiation: External beam radiation (standard); Radiation: External beam radiation (hyperfractionated)

• Registration Number: NCT03509012
• Lead Sponsor: AstraZeneca

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

Detailed Description

This study will initially treat up to approximately 300 patients with advanced solid tumors at approximately 30 sites, worldwide. The study will be composed of a dose-limiting toxicity (DLT) assessment phase (Part A) and an expansion phase (Part B).

Study Timeline

• Study First Submitted: 2018-03-12
• Study First Submitted QC: 2018-04-25
• Study First Posted: 2018-04-26
• Study Start: 2018-05-02
• Primary Completion: 2020-12-31
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-20
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SCLC Arm 1	Carboplatin (dose level 2)	Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
SCLC Arm 1	Etoposide (dose level 2)	Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
HNSCC Arm 1	External beam radiation (dose level 1)	Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
NSCLC Arm 1	Cisplatin (dose level 1)	Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
NSCLC Arm 3	External beam radiation (dose level 2)	Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
HNSCC Arm 1	Durvalumab	Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
HNSCC Arm 1	Cisplatin (dose level 4)	Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
NSCLC Arm 1	External beam radiation (dose level 2)	Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
SCLC Arm 1	Durvalumab	Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
SCLC Arm 2	Etoposide (dose level 2)	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
NSCLC Arm 1	Etoposide (dose level 1)	Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
NSCLC Arm 2	External beam radiation (dose level 2)	Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
NSCLC Arm 2	Carboplatin (dose level 1)	Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
NSCLC Arm 3	Durvalumab	Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
NSCLC Arm 3	Carboplatin (dose level 2)	Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
NSCLC Arm 3	Cisplatin (dose level 2)	Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
SCLC Arm 1	Cisplatin (dose level 3)	Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
SCLC Arm 1	External beam radiation (standard)	Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
NSCLC Arm 3	Pemetrexed	Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
SCLC Arm 2	Cisplatin (dose level 3)	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
SCLC Arm 3	Cisplatin (dose level 3)	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.
SCLC Arm 3	Etoposide (dose level 2)	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.
SCLC Arm 3	External beam radiation (standard)	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.
SCLC Arm 2	Carboplatin (dose level 2)	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
SCLC Arm 3	Carboplatin (dose level 2)	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.
SCLC Arm 4	Tremelimumab	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.
SCLC Arm 4	Etoposide (dose level 2)	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.
SCLC Arm 3	Durvalumab	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.
SCLC Arm 4	Carboplatin (dose level 2)	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.
SCLC Arm 2	External beam radiation (hyperfractionated)	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
SCLC Arm 4	Cisplatin (dose level 3)	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.
SCLC Arm 4	External beam radiation (hyperfractionated)	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.
NSCLC Arm 2	Durvalumab	Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
NSCLC Arm 1	Durvalumab	Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
NSCLC Arm 2	Paclitaxel	Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
SCLC Arm 2	Durvalumab	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
SCLC Arm 3	Tremelimumab	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.
SCLC Arm 4	Durvalumab	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.

Primary Outcome Measures

Name	Time	Method
Number of subjects with Adverse Events (AEs)	From first dose of durvalumab up to 90 days after the last dose of study treatment
Number of subjects with Dose Limiting Toxicities (DLTs)	From first dose of durvalumab until 28 days after completion of radiation therapy

Secondary Outcome Measures

Name	Time	Method
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.	The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression.
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.
Duration of response (DoR)	From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.	Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
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.	Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Disease control rate (DCR)	From first dose until disease progression, at 18 weeks and 48 weeks.
Disease-free survival (DFS)	From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.

Trial Locations

Locations (1)

Research Site; 🇨🇳 Taoyuan City, Taiwan