Immunotherapy + Chemoradiation for Cancer

(CLOVER Trial)

Recruiting at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Disqualifiers: Autoimmune disorders, Brain metastases, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

105 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Eligibility Criteria

This trial is for adults with advanced solid tumors, including various types of lung and oral cancers. Participants must have a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory, weigh over 30 kg, have at least one measurable lesion not previously treated with radiation, and no prior immune therapy. Exclusions include multiple primary malignancies, brain metastases, autoimmune disorders, certain specific cancer exclusions per cohort (e.g., unresectable head and neck cancers), paraneoplastic syndromes of autoimmune nature, mixed histology lung cancers, active infections like TB or HIV.

Inclusion Criteria

I have never received immune therapy or cancer vaccines.

I weigh more than 30 kg.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have active infections like TB, hepatitis B/C, or HIV.

I have an autoimmune-related syndrome caused by my cancer.

My head and neck cancer is not in the mouth, voice box, throat, or below the throat and its origin is known.

Treatment Details

Interventions

• Cisplatin
• Durvalumab
• Etoposide
• External beam radiation
• Paclitaxel
• Pemetrexed
• Tremelimumab

Trial Overview The study tests the safety and effectiveness of durvalumab alone or combined with tremelimumab alongside chemoradiation therapies such as Etoposide, Pemetrexed, Carboplatin/Cisplatin at varying doses levels paired with external beam radiation (standard/hyperfractionated). It's an early-phase trial to see how well patients tolerate this combination treatment for their advanced solid tumors.

Participant Groups

Group I: SCLC Arm 4 Experimental Treatment 6 Interventions

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.

Group II: SCLC Arm 3 Experimental Treatment 6 Interventions

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.

Group III: SCLC Arm 2 Experimental Treatment 5 Interventions

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

Group IV: SCLC Arm 1 Experimental Treatment 5 Interventions

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

Group V: NSCLC Arm 3 Experimental Treatment 5 Interventions

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

Group VI: NSCLC Arm 2 Experimental Treatment 4 Interventions

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

Group VII: NSCLC Arm 1 Experimental Treatment 4 Interventions

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

Group VIII: HNSCC Arm 1 Experimental Treatment 3 Interventions

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

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology