Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)

AstraZeneca

Status and phase: Completed; Phase 1

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

Treatments: Drug: Carboplatin (dose level 1); Drug: Cisplatin (dose level 3); Drug: Cisplatin (dose level 1); Drug: Cisplatin (dose level 4); Radiation: External beam radiation (dose level 2); Drug: Cisplatin (dose level 2); Drug: Durvalumab; Drug: Paclitaxel; Radiation: External beam radiation (hyperfractionated); Drug: Pemetrexed; Drug: Etoposide (dose level 2); Drug: Etoposide (dose level 1); Drug: Tremelimumab; Drug: Carboplatin (dose level 2); Radiation: External beam radiation (standard); Radiation: External beam radiation (dose level 1)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03509012

D933BC00001

2017-002242-77 (EudraCT Number)

Details and patient eligibility

About

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

Full 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).

Enrollment: 105 patients

Sex: All

Ages: 18 to 110 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

105 participants in 8 patient groups

HNSCC Arm 1

Experimental group

Description:

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

Treatment:

Radiation: External beam radiation (dose level 1)

Drug: Durvalumab

Drug: Cisplatin (dose level 4)

NSCLC Arm 1

Experimental group

Description:

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

Treatment:

Drug: Etoposide (dose level 1)

Drug: Durvalumab

Radiation: External beam radiation (dose level 2)

Drug: Cisplatin (dose level 1)

NSCLC Arm 2

Experimental group

Description:

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

Treatment:

Drug: Paclitaxel

Drug: Durvalumab

Radiation: External beam radiation (dose level 2)

Drug: Carboplatin (dose level 1)

NSCLC Arm 3

Experimental group

Description:

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

Treatment:

Drug: Carboplatin (dose level 2)

Drug: Pemetrexed

Drug: Cisplatin (dose level 2)

Drug: Durvalumab

Radiation: External beam radiation (dose level 2)

SCLC Arm 1

Experimental group

Description:

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

Treatment:

Radiation: External beam radiation (standard)

Drug: Carboplatin (dose level 2)

Drug: Etoposide (dose level 2)

Drug: Durvalumab

Drug: Cisplatin (dose level 3)

SCLC Arm 2

Experimental group

Description:

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

Treatment:

Drug: Carboplatin (dose level 2)

Drug: Etoposide (dose level 2)

Radiation: External beam radiation (hyperfractionated)

Drug: Durvalumab

Drug: Cisplatin (dose level 3)

SCLC Arm 3

Experimental group

Description:

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.

Treatment:

Radiation: External beam radiation (standard)

Drug: Carboplatin (dose level 2)

Drug: Tremelimumab

Drug: Etoposide (dose level 2)

Drug: Durvalumab

Drug: Cisplatin (dose level 3)

SCLC Arm 4

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin (dose level 2)

Drug: Tremelimumab

Drug: Etoposide (dose level 2)

Radiation: External beam radiation (hyperfractionated)

Drug: Durvalumab

Drug: Cisplatin (dose level 3)