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Chemotherapy and Immunotherapy in Extensive-Stage Small-Cell Lung Cancer With Thoracic Radiotherapy (CHEST RT)

Primary Purpose

Extensive-Stage Small-Cell Lung Cancer

Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Thoracic Radiotherapy
Etoposide with Carboplatin or Cisplatin
Durvalumab
Sponsored by
Trans Tasman Radiation Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extensive-Stage Small-Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provided written informed consent Histologically or cytologically documented ES-ECLC Thoracic disease deemed suitable for radiation therapy following initial systemic therapy If brain metastases present, then they are to be; asymptomatic without steroid therapy may be included or have required treatment (radiotherapy and/or surgery) and are clinically stable and patient is on a stable or reducing steroid dose of no more than dexamethasone 4mg/day (or equivalent) Patients must be considered suitable to receive platinum-based chemotherapy regimen as first-line treatment for ES-SCLC ECOG performance-status score of 0 or 1 at registration Life expectancy ≥ 12 weeks at registration Body weight > 30 kg No prior exposure to immune-mediated therapy including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed cell death-1, anti-programmed cell death ligand-1, and anti-programmed cell death ligand-2 antibodies, excluding therapeutic anticancer vaccines Adequate organ and marrow function as defined in the Protocol Female patients who; are willing to use adequate contraceptive measures until 90 days after the final dose of trial treatment are not breast feeding have a negative pregnancy test prior at registration if of child bearing potential or have evidence of non-child bearing potential by fulfilling the criteria as stated in the Protocol at screening Exclusion Criteria: Treatment with any of the following: Concurrent chemotherapy (not relevant to patients registered prior to cycle 2 who will have received a cycle of platinum/etoposide chemotherapy), investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable An investigational product during the last 4 weeks High dose radiotherapy to the chest prior to systemic therapy precluding further thoracic radiation therapy. Radiation therapy outside of the chest for palliative care (i.e., bone metastasis) is allowed but must be completed before first dose of the trial medication Immunosuppressive medication within 14 days before the first dose of durvalumab. Some exceptions apply Live, attenuated vaccine within 30 days prior to the first dose of durvalumab Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of Durvalumab. Surgical procedures to obtain a lung cancer diagnosis or for palliation are allowed Medical contraindication to, known allergy or hypersensitivity to durvalumab, etoposide, carboplatin (patients with allergy/hypersensitivity to carboplatin may receive cisplatin), cisplatin, or any of their excipients History of allogeneic organ transplantation Has a para-neoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS. Patients with hyponatraemia considered due to SIADH syndrome are eligible Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis. Some exceptions apply Interstitial lung disease/pulmonary fibrosis. Patients with emphysema and associated limited areas of pulmonary fibrosis are eligible Uncontrolled intercurrent illness History of another primary malignancy. Some exceptions apply History of leptomeningeal carcinomatosis History of active primary immunodeficiency Patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab

Sites / Locations

  • Westmead HospitalRecruiting
  • Blacktown HospitalRecruiting
  • Liverpool HospitalRecruiting
  • Royal Brisbane and Women's HospitalRecruiting
  • Princess Alexandra HospitalRecruiting
  • Peter MacCallum Cancer CentreRecruiting
  • St. Vincent's HospitalRecruiting
  • Austin HealthRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Participants will receive Durvalumab concurrently with chemotherapy (etoposide with carboplatin or cisplatin) for 4 cycles.

Outcomes

Primary Outcome Measures

Safety of chemo-immunotherapy with concurrent thoracic radiotherapy
Group 1 and Group 2 will be compared for the presence of toxicity, whereby the proportion of grade 3 or higher pneumonitis and grade 3 or higher oesophagitis will be monitored using the NCI Common Terminology Criteria for Adverse Events v5.
Feasibility of chemo-immunotherapy with concurrent thoracic radiotherapy
Group 1 and Group 2 will be compared for the proportion of participants which received concurrent radiotherapy vs the proportion of participants which did not receive concurrent radiotherapy. The two groups will also be assessed by the proportion of participants in which discontinued thoracic radiotherapy.

Secondary Outcome Measures

Overall Survival
Overall survival will be defined as the time from the Cycle 1 day 1 of chemotherapy until the date of death by any cause. Participants who are alive by the analysis time point will be censored at the trial close out date.
Progression free survival
Progression free survival will be defined as the time from Cycle 1 Day 1 of chemotherapy until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. Participants who are alive or have not progressed by the analysis time point will be censored at the latest of the dates contributing to a particular overall visit assessment.
Patterns of failure
Patterns of failure assessed by the proportion of patients with first site of failure in: Thoracic, Extra-thoracic or cranial sites, seen on imaging (CT/MRI) and assessed by iRECIST and/or RANO-BM criteria. The first site of treatment relapse will be collected and categorised as thoracic, extra-thoracic or cranial.
Time to local failure and local control
Time to thoracic local failure and proportion of participants with thoracic local control.

Full Information

First Posted
February 9, 2023
Last Updated
September 5, 2023
Sponsor
Trans Tasman Radiation Oncology Group
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT05796089
Brief Title
Chemotherapy and Immunotherapy in Extensive-Stage Small-Cell Lung Cancer With Thoracic Radiotherapy
Acronym
CHEST RT
Official Title
A Phase II Study of Platinum and Etoposide Chemotherapy, Durvalumab With Thoracic Radiotherapy in the First Line Treatment of Patients With Extensive-stage Small-cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Actual)
Primary Completion Date
September 30, 2027 (Anticipated)
Study Completion Date
February 28, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trans Tasman Radiation Oncology Group
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, multi-centre, single arm, phase 2, open label clinical trial of patients with untreated extensive-stage small-cell lung cancer (ES-SCLC) suitable for first-line platinum-based chemotherapy. The aim of the trial is to assess safety, feasibility and describe efficacy of the addition of concurrent thoracic radiotherapy to usual treatment of chemotherapy and immunotherapy (durvalumab) in patients with ES-SCLC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extensive-Stage Small-Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Participants will receive Durvalumab concurrently with chemotherapy (etoposide with carboplatin or cisplatin) for 4 cycles.
Intervention Type
Radiation
Intervention Name(s)
Thoracic Radiotherapy
Other Intervention Name(s)
Thoracic Radiation Therapy
Intervention Description
Participants will receive thoracic radiotherapy to a dose of 30 Gray (Gy) in 10 fractions (3 Gy per day) concurrently with cycle 3 or 4 of chemo-immunotherapy (Group 1). Participants who are unsuitable for concurrent radiotherapy may receive consolidation radiotherapy. Consolidation thoracic radiotherapy will be administered to a dose of 30 Gy in 10 fractions, following 4 cycles of chemo-immunotherapy (Group 2). Treatment fractions will be delivered daily, where treatment should be completed within 15 days (9-10 fractions a fortnight).
Intervention Type
Drug
Intervention Name(s)
Etoposide with Carboplatin or Cisplatin
Other Intervention Name(s)
Platinum + Etoposide, EP Chemotherapy
Intervention Description
The chemotherapy in this study is a standard treatment for extensive-stage small-cell lung cancer (EC-SCLC). The combination of chemotherapy (etoposide + carboplatin or etoposide + cisplatin) which the participant will receive is dependent on what is standard at the treatment centre. Chemotherapy will be administered via an intravenous infusion every 3 weeks (21 days) for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
IMFINZI, MEDI4736
Intervention Description
The immunotherapy in this study is a standard treatment for ES-SCLC. Participants will receive a dose of 1500 mg of Durvalumab via an intravenous infusion every 3 weeks (21 days) for 4 cycles, concurrently with chemotherapy. A 1500 mg maintenance dose of Durvalumab will administered every 4 weeks after completion of chemotherapy (monotherapy).
Primary Outcome Measure Information:
Title
Safety of chemo-immunotherapy with concurrent thoracic radiotherapy
Description
Group 1 and Group 2 will be compared for the presence of toxicity, whereby the proportion of grade 3 or higher pneumonitis and grade 3 or higher oesophagitis will be monitored using the NCI Common Terminology Criteria for Adverse Events v5.
Time Frame
From date of consent to 90 days after trial treatment is discontinued
Title
Feasibility of chemo-immunotherapy with concurrent thoracic radiotherapy
Description
Group 1 and Group 2 will be compared for the proportion of participants which received concurrent radiotherapy vs the proportion of participants which did not receive concurrent radiotherapy. The two groups will also be assessed by the proportion of participants in which discontinued thoracic radiotherapy.
Time Frame
From date of consent to 90 days after trial treatment is discontinued
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival will be defined as the time from the Cycle 1 day 1 of chemotherapy until the date of death by any cause. Participants who are alive by the analysis time point will be censored at the trial close out date.
Time Frame
12 months
Title
Progression free survival
Description
Progression free survival will be defined as the time from Cycle 1 Day 1 of chemotherapy until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. Participants who are alive or have not progressed by the analysis time point will be censored at the latest of the dates contributing to a particular overall visit assessment.
Time Frame
6 and 12 months
Title
Patterns of failure
Description
Patterns of failure assessed by the proportion of patients with first site of failure in: Thoracic, Extra-thoracic or cranial sites, seen on imaging (CT/MRI) and assessed by iRECIST and/or RANO-BM criteria. The first site of treatment relapse will be collected and categorised as thoracic, extra-thoracic or cranial.
Time Frame
From date of registration until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 152 weeks
Title
Time to local failure and local control
Description
Time to thoracic local failure and proportion of participants with thoracic local control.
Time Frame
6 and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provided written informed consent Histologically or cytologically documented ES-ECLC Thoracic disease deemed suitable for radiation therapy following initial systemic therapy If brain metastases present, then they are to be; asymptomatic without steroid therapy may be included or have required treatment (radiotherapy and/or surgery) and are clinically stable and patient is on a stable or reducing steroid dose of no more than dexamethasone 4mg/day (or equivalent) Patients must be considered suitable to receive platinum-based chemotherapy regimen as first-line treatment for ES-SCLC ECOG performance-status score of 0 or 1 at registration Life expectancy ≥ 12 weeks at registration Body weight > 30 kg No prior exposure to immune-mediated therapy including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed cell death-1, anti-programmed cell death ligand-1, and anti-programmed cell death ligand-2 antibodies, excluding therapeutic anticancer vaccines Adequate organ and marrow function as defined in the Protocol Female patients who; are willing to use adequate contraceptive measures until 90 days after the final dose of trial treatment are not breast feeding have a negative pregnancy test prior at registration if of child bearing potential or have evidence of non-child bearing potential by fulfilling the criteria as stated in the Protocol at screening Exclusion Criteria: Treatment with any of the following: Concurrent chemotherapy (not relevant to patients registered prior to cycle 2 who will have received a cycle of platinum/etoposide chemotherapy), investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable An investigational product during the last 4 weeks High dose radiotherapy to the chest prior to systemic therapy precluding further thoracic radiation therapy. Radiation therapy outside of the chest for palliative care (i.e., bone metastasis) is allowed but must be completed before first dose of the trial medication Immunosuppressive medication within 14 days before the first dose of durvalumab. Some exceptions apply Live, attenuated vaccine within 30 days prior to the first dose of durvalumab Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of Durvalumab. Surgical procedures to obtain a lung cancer diagnosis or for palliation are allowed Medical contraindication to, known allergy or hypersensitivity to durvalumab, etoposide, carboplatin (patients with allergy/hypersensitivity to carboplatin may receive cisplatin), cisplatin, or any of their excipients History of allogeneic organ transplantation Has a para-neoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS. Patients with hyponatraemia considered due to SIADH syndrome are eligible Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis. Some exceptions apply Interstitial lung disease/pulmonary fibrosis. Patients with emphysema and associated limited areas of pulmonary fibrosis are eligible Uncontrolled intercurrent illness History of another primary malignancy. Some exceptions apply History of leptomeningeal carcinomatosis History of active primary immunodeficiency Patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bridget Rooney
Phone
+61 2 40143911
Email
CHESTRT@trog.com.au
First Name & Middle Initial & Last Name or Official Title & Degree
Eric Hau
Phone
+61 2 9881 8421
Email
eric.hau@health.nsw.gov.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Hau
Organizational Affiliation
Westmead/Blacktown Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sagun Parakh
Organizational Affiliation
Austin Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Westmead Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Harriet Gee
Facility Name
Blacktown Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Hau
Facility Name
Liverpool Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shalini Vinod
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Bettington
Facility Name
Princess Alexandra Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margot Lehman
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Harden
Facility Name
St. Vincent's Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Moore
Facility Name
Austin Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sagun Parakh

12. IPD Sharing Statement

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Chemotherapy and Immunotherapy in Extensive-Stage Small-Cell Lung Cancer With Thoracic Radiotherapy

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