Clinical trial NCT05796089: Chemotherapy and Immunotherapy in Extensive-Stage Small-Cell Lung Cancer With Thoracic Radiotherapy
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Extensive-Stage Small-Cell Lung Cancer
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2023-04-03
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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;

  1. asymptomatic without steroid therapy may be included or
  2. 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;

  1. are willing to use adequate contraceptive measures until 90 days after the final dose of trial treatment
  2. are not breast feeding
  3. 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:

  1. 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
  2. An investigational product during the last 4 weeks
  3. 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
  4. Immunosuppressive medication within 14 days before the first dose of durvalumab. Some exceptions apply
  5. Live, attenuated vaccine within 30 days prior to the first dose of durvalumab
  6. 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

Primary outcomes:
measure: Safety of chemo-immunotherapy with concurrent thoracic radiotherapy
timeFrame: From date of consent to 90 days after trial treatment is discontinued
measure: Feasibility of chemo-immunotherapy with concurrent thoracic radiotherapy
timeFrame: From date of consent to 90 days after trial treatment is discontinued
Secondary outcomes:
measure: Overall Survival
timeFrame: 12 months
measure: Progression free survival
timeFrame: 6 and 12 months
measure: Patterns of failure
timeFrame: 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
measure: Time to local failure and local control
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
Study officials:
affiliation: Westmead/Blacktown Hospital
name: Eric Hau
role: STUDY_CHAIR
affiliation: Austin Health
name: Sagun Parakh
role: PRINCIPAL_INVESTIGATOR
References: