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

May 10, 2024 updated by: AstraZeneca

A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

105

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Koto-ku, Japan, 135-8550
        • Research Site
      • Sunto-gun, Japan, 411-8777
        • Research Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Research Site
      • Seoul, Korea, Republic of, 05505
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Research Site
  • Spain
      • Badalona, Spain, 08916
        • Research Site
      • Madrid, Spain, 28007
        • Research Site
      • Málaga, Spain, 29010
        • Research Site
  • Taiwan
      • Taichung, Taiwan, 40705
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
      • Taipei, Taiwan, 112
        • Research Site
      • Taoyuan City, Taiwan, 333
        • Research Site
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
    • Texas
      • Houston, Texas, United States, 77090
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HNSCC Arm 1
Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Drug: Cisplatin (dose level 4)
IV
Radiation: External beam radiation (dose level 1)
radiation therapy
Experimental: NSCLC Arm 1
Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Drug: Etoposide (dose level 1)
IV
Radiation: External beam radiation (dose level 2)
radiation therapy
Drug: Cisplatin (dose level 1)
IV
Experimental: NSCLC Arm 2
Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
Drug: Paclitaxel
IV
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Radiation: External beam radiation (dose level 2)
radiation therapy
Drug: Carboplatin (dose level 1)
IV
Experimental: NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Radiation: External beam radiation (dose level 2)
radiation therapy
Drug: Carboplatin (dose level 2)
IV
Drug: Pemetrexed
IV
Drug: Cisplatin (dose level 2)
IV
Experimental: SCLC Arm 1
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Drug: Carboplatin (dose level 2)
IV
Drug: Cisplatin (dose level 3)
IV
Drug: Etoposide (dose level 2)
IV
Radiation: External beam radiation (standard)
radiation therapy
Experimental: SCLC Arm 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
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Drug: Carboplatin (dose level 2)
IV
Drug: Cisplatin (dose level 3)
IV
Drug: Etoposide (dose level 2)
IV
Radiation: External beam radiation (hyperfractionated)
radiation therapy
Experimental: SCLC Arm 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.
Drug: Durvalumab
IV (intravenous)
Other Names:
  • MEDI4736
Drug: Carboplatin (dose level 2)
IV
Drug: Cisplatin (dose level 3)
IV
Drug: Etoposide (dose level 2)
IV
Radiation: External beam radiation (standard)
radiation therapy
Drug: Tremelimumab
IV
Experimental: SCLC Arm 4
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
IV (intravenous)
Other Names:
  • MEDI4736
Drug: Carboplatin (dose level 2)
IV
Drug: Cisplatin (dose level 3)
IV
Drug: Etoposide (dose level 2)
IV
Radiation: External beam radiation (hyperfractionated)
radiation therapy
Drug: Tremelimumab
IV

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 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.
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)
Time Frame: From first dose until death due to any cause through study completion, up to 4 years
From first dose until death due to any cause through study completion, up to 4 years
Objective response rate (ORR)
Time Frame: 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).
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)
Time Frame: 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.
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)
Time Frame: 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.
From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
Disease control rate (DCR)
Time Frame: From first dose until disease progression, at 18 weeks and 48 weeks.
From first dose until disease progression, at 18 weeks and 48 weeks.
Disease-free survival (DFS)
Time Frame: From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.
From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2018

Primary Completion (Actual)

December 31, 2020

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

March 12, 2018

First Submitted That Met QC Criteria

April 25, 2018

First Posted (Actual)

April 26, 2018

Study Record Updates

Last Update Posted (Estimated)

May 13, 2024

Last Update Submitted That Met QC Criteria

May 10, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D933BC00001
  • 2017-002242-77 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing 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.

IPD Sharing 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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