Adding short-course high-dose radiation to standard treatment for people with oligometastatic non-small cell lung cancer

Addition of Hypofractionated High Dose Radiation in Oligometastatic Disease - An Open Label Randomized Phase III Trial Comparing Up-front Radiation in Oligometastatic Non-small Cell Lung Cancer (NSCLC) and Systemic Treatment With Systemic Treatment Alone

This trial will test whether giving focused high-dose radiation to all known tumors along with standard systemic therapy helps people with non-small cell lung cancer who have five or fewer metastases.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vastra Gotaland Region (other gov)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 6 sites (Gothenburg and 5 other locations)
• Trial ID: NCT06141070 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label phase III trial that randomizes patients 2:1 to receive standard first-line systemic therapy with or without additional hypofractionated high-dose radiotherapy to all known lesions. Radiotherapy is planned during the first three months of systemic therapy, preferably using SBRT/SRT/SRS but allowing conventional radiotherapy when needed. Systemic therapy follows local practice (chemotherapy, chemoimmunotherapy, or immunotherapy) with response assessed after three to four cycles and radiologic follow-up every three months. Patients are stratified by performance status, gender, and systemic treatment strategy.

Who should consider this trial

Good fit: Adults with histologically confirmed NSCLC, stage IV with five or fewer metastases, WHO performance status 0–2, no prior systemic or radiotherapy for metastatic disease, and lesions amenable to SBRT or conventional radiotherapy are ideal candidates.

Not a fit: Patients with more than five metastases, poor performance status, lesions not suitable for targeted radiotherapy, or who have already received systemic therapy for metastatic NSCLC are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding targeted high-dose radiotherapy could improve local tumor control and extend progression-free and possibly overall survival for patients with limited metastatic NSCLC.

How similar studies have performed: Earlier randomized phase II trials and phase II data in oligometastatic NSCLC and other cancers have suggested progression-free survival benefits from adding local ablative radiotherapy, but phase III confirmation is limited.

Eligibility criteria

Inclusion Criteria:

* Written informed consent obtained from the subject prior to performing any protocol- related procedures, including screening procedures

  * Histological or cytological diagnosis of NSCLC
  * Stage IV disease with ≤5 metastases (not including primary tumour or mediastinal nodes, N1-N3)
  * Patient deemed fit for first line chemoimmunotherapy, immunotherapy or chemotherapy
  * Extra-thoracic metastases accessible for stereotactic body radiotherapy (SBRT)
  * Thoracic tumour(s) accessible for SBRT or conventional radiotherapy
  * Received no prior systemic treatment or radiation therapy for NSCLC (previous adjuvant systemic therapy is allowed)
  * Age \> 18 years at time of study entry, no upper age limit
  * WHO performance status 0-2
  * Adequate normal organ and marrow function Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects.

    * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria:

* • Solitary brain lesion or contralateral lung lesion as the only distant metastasis

  * Participation in another clinical study with an investigational product during the last 4 weeks
  * Patients with EGFR+, ALK+, ROS1+ disease or any other genetic alteration that would result in a TKI based first line treatment (i.e. first line treatment not being chemoimmuno- or immunotherapy)
  * Malignant pleural fluid, or ascites (malignant cells or clinical judgement) or excessive fluid hampering radiation according to protocol
  * Leptomeningeal disease
  * Pulmonary fibrosis making protocol stipulated treatment hazardous (low grade radiologic findings are allowed as assessed by the investigator)
  * Not deemed fit for standard first line systemic therapy
  * Second primary residual malignancy. Other malignancy diagnosed and treated \> 2 years ago without relapse and deemed to have a low likelihood of relapse is allowed. (Carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin \< 2 years are allowed, as is other low-grade malignancy with low likelihood of becoming metastatic or impact on survival e.g. low-grade prostate cancer not in need of treatment)
  * Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of systemic therapy
  * Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Where this trial is running

Gothenburg and 5 other locations

• Dept of Oncology — Gothenburg, Sweden (RECRUITING)
• Dept of pulmonary medicine — Linköping, Sweden (NOT_YET_RECRUITING)
• Dept of pulmonary medicine — Lund, Sweden (NOT_YET_RECRUITING)
• Dept of Oncology — Stockholm, Sweden (RECRUITING)
• Dept. of Oncology — Umeå, Sweden (RECRUITING)
• Dept. of Oncology — Uppsala, Sweden (RECRUITING)

Study contacts

• Study coordinator: Andreas Hallqvist

Conditions: Non Small Cell Lung Cancer