Immunotherapy + Chemoradiation for Cancer

(CLOVER Trial)

No longer recruiting at 14 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: AstraZeneca
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of combining immunotherapy drugs, such as durvalumab and tremelimumab, with chemoradiation for individuals with advanced solid tumors. It specifically examines treatments for certain cancers, including small-cell lung cancer (SCLC), head and neck cancer (HNSCC), and non-small-cell lung cancer (NSCLC). Participants may qualify if they have been diagnosed with any of these cancers in advanced stages and have not received prior immune-based treatments. The trial aims to determine how well these treatments work together and whether patients can tolerate them safely. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that durvalumab, when combined with radiation and other drugs, is generally well-tolerated by people with head and neck cancer. Studies have found that combining durvalumab and cisplatin with radiation did not lead to unexpected side effects, indicating relative safety for most patients.

For non-small-cell lung cancer (NSCLC), researchers have extensively studied durvalumab combined with cisplatin and etoposide. The data show that common side effects include tiredness and nausea, but these are usually manageable. Using durvalumab with carboplatin and paclitaxel in NSCLC also resulted in similar manageable side effects.

Another combination, pemetrexed with carboplatin or cisplatin and radiation, has been found to be tolerable. Most side effects, like low blood counts and tiredness, were not severe.

In summary, these treatments have demonstrated a good safety profile in previous studies. However, discussing potential risks with a healthcare provider remains important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine immunotherapy with chemoradiation to attack cancer in multiple ways. Unlike standard treatments that primarily rely on chemotherapy and radiation, these investigational treatments use drugs like Durvalumab and Tremelimumab, which are immune checkpoint inhibitors that help the immune system recognize and destroy cancer cells more effectively. Additionally, the option to switch from cisplatin to carboplatin offers flexibility for patients who may not tolerate certain chemotherapy drugs well. This multi-faceted approach aims to increase effectiveness and minimize side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that using durvalumab with cisplatin and radiation may help treat head and neck cancer. The CLOVER study found this combination safe and effective against tumors. One arm of this trial will test durvalumab with cisplatin and radiation for patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC).

For lung cancer, the PACIFIC trial found that durvalumab helped patients live longer when used after chemotherapy and radiation. Different arms of this trial will explore combinations of durvalumab with other drugs like cisplatin and etoposide, or carboplatin and paclitaxel, for advanced non-small-cell lung cancer (NSCLC). Additionally, another arm will investigate the use of carboplatin with pemetrexed or cisplatin with pemetrexed for NSCLC. These studies suggest that these treatment combinations could effectively target advanced cancers.678910

Are You a Good Fit for This Trial?

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 know my HPV status for my throat cancer.
See 2 more

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.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-limiting toxicity (DLT) assessment

Initial phase to assess the safety and tolerability of the treatment regimen

8 weeks

Expansion

Participants receive the study treatment to further evaluate safety and efficacy

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
8Treatment groups
Experimental Treatment
Group I: SCLC Arm 4Experimental Treatment6 Interventions
Group II: SCLC Arm 3Experimental Treatment6 Interventions
Group III: SCLC Arm 2Experimental Treatment5 Interventions
Group IV: SCLC Arm 1Experimental Treatment5 Interventions
Group V: NSCLC Arm 3Experimental Treatment5 Interventions
Group VI: NSCLC Arm 2Experimental Treatment4 Interventions
Group VII: NSCLC Arm 1Experimental Treatment4 Interventions
Group VIII: HNSCC Arm 1Experimental Treatment3 Interventions

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

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Approved in European Union as Platinol for:
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Approved in United States as Platinol for:
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Approved in Canada as Platinol for:
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Approved in Japan as Platinol for:

Find a Clinic Near You

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

Citations

Efficacy and safety of first-line pemetrexed plus carboplatin ...Treatment with pemetrexed combined with cisplatin demonstrated non-inferior efficacy against cisplatin-gemcitabine in a phase III trial in metastatic NSCLC [4].
Pemetrexed for advanced stage nonsquamous non-small ...Four phase II studies investigated the combination of pemetrexed with cisplatin or carboplatin for nonsquamous NSCLC first-line treatment [Zinner et al. 2005].
Assessing effectiveness of first-line carboplatin, ...The median overall survival from start of therapy was 11 months (95% confidence interval 9-12 months). Conclusions: In routine clinical practice ...
Comparison of Carboplatin Plus Pemetrexed Followed by ...This trial demonstrated a superior outcome for the carboplatin-based doublet in terms of OS, PFS, and response rate, although its effectiveness ...
Pemetrexed plus carboplatin versus ...The median PFS in the data from the GOIRC 02-2006 study was 3.6 months in the pemetrexed–carboplatin arm versus 3.8 months in the pemetrexed arm, the median OS ...
Phase 2 Study of Pemetrexed plus Carboplatin, or ...The safety profile of pemetrexed, its approved use with cisplatin in first-line nonsquamous NSCLC, and its utility in the maintenance setting suggest that ...
Alimta, Carboplatin and Radiation Therapy for Non Small ...To determine the safety of Alimta when used with chemoradiation in inoperable non small cell lung cancer. Detailed Description. To determine the maximal ...
Toxicity and Response of Pemetrexed Plus Carboplatin or ...Pemetrexed is an effective and a tolerable drug in advanced non-small cell lung cancer (NSCLC). This study sought to ascertain maximum tolerated dose (MTD) ...
Alimta, Carboplatin and Radiation Therapy for Non Small Cell ...To determine the safety of Alimta when used with chemoradiation in inoperable non small cell lung cancer.
A Phase I Study of Pemetrexed, Carboplatin, and Concurrent ...All dose levels were tolerable for regimen 1 (n = 18: 15 NSCLC and 3 esophageal cancers) and regimen 2 (n = 12: all NSCLC). In regimen 1, one dose-limiting ...
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