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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03509012
Recruitment Status : Active, not recruiting
First Posted : April 26, 2018
Last Update Posted : September 29, 2020
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell of Head and Neck Carcinoma, Non-Small-Cell Lung Small Cell Lung Carcinoma Drug: Durvalumab Drug: Tremelimumab Drug: Cisplatin (dose level 4) Drug: Cisplatin (dose level 3) Drug: Carboplatin (dose level 1) Drug: Carboplatin (dose level 2) Drug: Etoposide (dose level 1) Drug: Etoposide (dose level 2) Drug: Paclitaxel Drug: Pemetrexed Radiation: External beam radiation (dose level 1) Radiation: External beam radiation (dose level 2) Radiation: External beam radiation (hyperfractionated) Drug: Cisplatin (dose level 1) Drug: Cisplatin (dose level 2) Radiation: External beam radiation (standard) Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : April 4, 2022
Estimated Study Completion Date : April 4, 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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: Durvalumab
IV (intravenous)
Other Name: MEDI4736

Drug: Carboplatin (dose level 1)
IV

Drug: Paclitaxel
IV

Radiation: External beam radiation (dose level 2)
radiation therapy

Experimental: NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
Drug: Durvalumab
IV (intravenous)
Other Name: MEDI4736

Drug: Carboplatin (dose level 2)
IV

Drug: Pemetrexed
IV

Radiation: External beam radiation (dose level 2)
radiation therapy

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 Name: MEDI4736

Drug: Cisplatin (dose level 3)
IV

Drug: Carboplatin (dose level 2)
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 Name: MEDI4736

Drug: Cisplatin (dose level 3)
IV

Drug: Carboplatin (dose level 2)
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 Name: MEDI4736

Drug: Tremelimumab
IV

Drug: Cisplatin (dose level 3)
IV

Drug: Carboplatin (dose level 2)
IV

Drug: Etoposide (dose level 2)
IV

Radiation: External beam radiation (standard)
radiation therapy

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 Name: MEDI4736

Drug: Tremelimumab
IV

Drug: Cisplatin (dose level 3)
IV

Drug: Carboplatin (dose level 2)
IV

Drug: Etoposide (dose level 2)
IV

Radiation: External beam radiation (hyperfractionated)
radiation therapy




Primary Outcome Measures :
  1. Number of subjects with Dose Limiting Toxicities (DLTs) [ Time Frame: From first dose of durvalumab until 28 days after completion of radiation therapy ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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. ]
  2. Overall Survival (OS) [ Time Frame: From first dose until death due to any cause through study completion, up to 4 years ]
  3. 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).

  4. 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.

  5. 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.

  6. Disease control rate (DCR) [ Time Frame: From first dose until disease progression, at 18 weeks and 48 weeks. ]
  7. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03509012


Locations
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United States, Arizona
Research Site
Tucson, Arizona, United States, 85719
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Texas
Research Site
Houston, Texas, United States, 77090
Japan
Research Site
Koto-ku, Japan, 135-8550
Research Site
Sunto-gun, Japan, 411-8777
Korea, Republic of
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 05505
Research Site
Seoul, Korea, Republic of, 135-710
Spain
Research Site
Badalona, Spain, 08916
Research Site
Madrid, Spain, 28007
Research Site
Málaga, Spain, 29010
Taiwan
Research Site
Taichung, Taiwan, 40705
Research Site
Taipei, Taiwan, 10002
Research Site
Taipei, Taiwan, 112
Research Site
Taoyuan City, Taiwan, 333
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03509012    
Other Study ID Numbers: D933BC00001
First Posted: April 26, 2018    Key Record Dates
Last Update Posted: September 29, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Durvalumab
Chemotherapy
Radiotherapy
HNSCC
NSCLC
SCLC
locally-advanced
limited stage
first line
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Small Cell Lung Carcinoma
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Paclitaxel
Etoposide
Cisplatin
Carboplatin
Etoposide phosphate
Pemetrexed
Durvalumab
Tremelimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents