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

Primary Purpose

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

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Durvalumab
Tremelimumab
Cisplatin (dose level 4)
Cisplatin (dose level 3)
Carboplatin (dose level 1)
Carboplatin (dose level 2)
Etoposide (dose level 1)
Etoposide (dose level 2)
Paclitaxel
Pemetrexed
External beam radiation (dose level 1)
External beam radiation (dose level 2)
External beam radiation (hyperfractionated)
Cisplatin (dose level 1)
Cisplatin (dose level 2)
External beam radiation (standard)
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Squamous Cell of Head and Neck focused on measuring Durvalumab, Chemotherapy, Radiotherapy, HNSCC, NSCLC, SCLC, locally-advanced, limited stage, first line

Eligibility Criteria

18 Years - 110 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

HNSCC Arm 1

NSCLC Arm 1

NSCLC Arm 2

NSCLC Arm 3

SCLC Arm 1

SCLC Arm 2

SCLC Arm 3

SCLC Arm 4

Arm Description

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

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

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

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

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

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

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.

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.

Outcomes

Primary Outcome Measures

Number of subjects with Dose Limiting Toxicities (DLTs)
Number of subjects with Adverse Events (AEs)

Secondary Outcome Measures

Progression-free survival (PFS)
Overall Survival (OS)
Objective response rate (ORR)
Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Best objective response (BoR)
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.
Duration of response (DoR)
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
Disease control rate (DCR)
Disease-free survival (DFS)

Full Information

First Posted
March 12, 2018
Last Updated
August 29, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT03509012
Brief Title
Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors
Acronym
CLOVER
Official Title
A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2, 2018 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
December 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Squamous Cell of Head and Neck, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
Keywords
Durvalumab, Chemotherapy, Radiotherapy, HNSCC, NSCLC, SCLC, locally-advanced, limited stage, first line

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HNSCC Arm 1
Arm Type
Experimental
Arm Description
Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
Arm Title
NSCLC Arm 1
Arm Type
Experimental
Arm Description
Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
Arm Title
NSCLC Arm 2
Arm Type
Experimental
Arm Description
Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
Arm Title
NSCLC Arm 3
Arm Type
Experimental
Arm Description
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
Arm Title
SCLC Arm 1
Arm Type
Experimental
Arm Description
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
Arm Title
SCLC Arm 2
Arm Type
Experimental
Arm 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
Arm Title
SCLC Arm 3
Arm Type
Experimental
Arm 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.
Arm Title
SCLC Arm 4
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
MEDI4736
Intervention Description
IV (intravenous)
Intervention Type
Drug
Intervention Name(s)
Tremelimumab
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin (dose level 4)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin (dose level 3)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Carboplatin (dose level 1)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Carboplatin (dose level 2)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Etoposide (dose level 1)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Etoposide (dose level 2)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
IV
Intervention Type
Radiation
Intervention Name(s)
External beam radiation (dose level 1)
Intervention Description
radiation therapy
Intervention Type
Radiation
Intervention Name(s)
External beam radiation (dose level 2)
Intervention Description
radiation therapy
Intervention Type
Radiation
Intervention Name(s)
External beam radiation (hyperfractionated)
Intervention Description
radiation therapy
Intervention Type
Drug
Intervention Name(s)
Cisplatin (dose level 1)
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin (dose level 2)
Intervention Description
IV
Intervention Type
Radiation
Intervention Name(s)
External beam radiation (standard)
Intervention Description
radiation therapy
Primary Outcome Measure Information:
Title
Number of subjects with Dose Limiting Toxicities (DLTs)
Time Frame
From first dose of durvalumab until 28 days after completion of radiation therapy
Title
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 Measure Information:
Title
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.
Title
Overall Survival (OS)
Time Frame
From first dose until death due to any cause through study completion, up to 4 years
Title
Objective response rate (ORR)
Description
Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Time Frame
From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Title
Best objective response (BoR)
Description
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.
Time Frame
From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Title
Duration of response (DoR)
Description
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
Time Frame
From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
Title
Disease control rate (DCR)
Time Frame
From first dose until disease progression, at 18 weeks and 48 weeks.
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
110 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Research Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Research Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
Research Site
City
Koto-ku
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Research Site
City
Sunto-gun
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Research Site
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Research Site
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
Facility Name
Research Site
City
Taoyuan City
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors

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