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Non-ablative Oligofractionated Radiation Therapy Before Surgical Transplantation As Radiovaccination (NORTh STAR)

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ClinicalTrials.gov Identifier: NCT04782752
Recruitment Status : Recruiting
First Posted : March 4, 2021
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
This is a prospective phase I study to determine the safety and feasibility of non-ablative oligofractionated radiation therapy (NORT) before lung transplantation for patients with underlying pulmonary malignancy. We hypothesize that heterogeneous dose distributions could generate a vaccination effect against the tumor by creating anti-tumoral immune response in the body and these patients may be immunized against their tumor which could reduce the risk of cancer recurrence after transplantation despite the anti-rejection medications required for the transplantation.

Condition or disease Intervention/treatment Phase
Transplant-Related Lung Cancer Radiation: Radiation: Varying Doses of RT Not Applicable

Detailed Description:

This study is designed to deliver short courses of radiation to the pulmonary malignancy followed by resection of the radiated tumor at the time of transplant.

The study is a 3+3 phase 1 study with incremental dose of radiation to determine the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) will be defined as grade 3+ radiation related toxicity. If one DLT is seen, then an additional 3 patients will be treated at the same dose level. If 2 or more DLT are seen at any given dose level, then the previous dose level will be defined as the MTD. A minimum of 3 patients and maximum of 18 patients will be included for the phase 1a. Due to the expected higher radiation risks in patients with end-stage ILD (group 1), these patients will be stratified separately from non-ILD patients (group 2, 3 and 4) during phase 1a. Dose tested are: 3 x 400 cGy, 3 x 600 cGy and 3 x 800 cGy for the ILD cohort and 3 x 800 cGy, 3 x 1000 cGy and 3 x 1200 cGy for the non-ILD cohort.

Once the MTD is determined, patients will proceed to phase 1b using the MTD determined in the phase 1a. ILD and non-ILD patients may have different MTD so two separate phase Ib cohorts will be conducted. A total of 12 patients will be included for each cohort in the phase 1b. The dose distribution will be administered using a standard homogenous dose distribution for tumors ≤2 cm, and an heterogeneous dose distribution for tumors >2 cm.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 radiation dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-ablative Oligofractionated Radiation Therapy Before Surgical Transplantation As Radiovaccination
Actual Study Start Date : March 30, 2021
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: Radiation

Patients will be differentiated into 4 groups:

  1. Patients with end-stage interstitial lung disease (ILD) and suspected stage I (up to 4 cm) primary lung cancer
  2. Patients with end-stage lung disease other than ILD (e.g. emphysema/COPD, cystic fibrosis and pulmonary hypertension) and suspected stage I (up to 4 cm) primary lung cancer
  3. Patients with multifocal primary lung cancer (e.g. multifocal adenocarcinoma) in the absence of nodal metastasis and distant metastasis.
  4. Patients with isolated pulmonary metastasis in the absence of other sites of malignancy (primary and metastatic).

For this study, different doses will be used for each different group depending on their tumour size. The first 3 patients will start with a dose of 4 Gy, for the ILD group, or 8 Gy, for the non ILD group. The doses are then increased incrementally until the dose limiting toxicity is reached.

Radiation: Radiation: Varying Doses of RT
3+3 radiation dose escalation model to see the maximum tolerated dose




Primary Outcome Measures :
  1. Maximum Tolerated Dose for Radiation [ Time Frame: Up to four years ]

    AEs will be graded by CTCAE. Maximum tolerated dose is the dose level do not result in fatal injury (grade 5 lung toxicity) or life-threatening or fatal treatment related toxicity (grade 4+).

    Safety will be determined by the absence of grade 3 or greater (G3+) complications related to radiation and the feasibility to list patients for transplantation one week after the end of radiation will be determined.



Secondary Outcome Measures :
  1. Patient Morbidity [ Time Frame: Up to four years ]
    NCI common toxicity scale

  2. Local recurrence [ Time Frame: Up to four years ]
    Documented radiographically



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

Inclusion Criteria:

  • Age ≥ 18
  • Patients with end-stage lung disease and suspected stage I primary lung cancer based on CT and PET scan not accessible to curative treatment, including surgery and ablative SBRT.
  • Patients with multifocal pulmonary malignancy, including multifocal lung adenocarcinoma, not accessible to curative treatment, including surgery and ablative SBRT.
  • Patients with isolated metastases in one or both lungs after complete resection of the primary tumor in the absence of other sites of metastatic disease, not accessible to curative treatment, including surgery and ablative SBRT.
  • Meet eligibility criteria for lung transplantation with the exception of the underlying malignancy.
  • Subjects must be able to understand the potential risks and benefits of the study and must be able to read and provide written, informed consent for the study.

Exclusion Criteria:

  • Age < 18
  • Mediastinal nodes metastasis demonstrated on EBUS-TBNA
  • Distant metastasis demonstrated on PET scan or brain imaging.
  • Failure to provide informed consent
  • Previous thoracic radiation resulting in significant mediastinal or chest wall overlap precluding re-irradiation
  • Any other medical condition that, in the opinion of the multidisciplinary team, may interfere with the subject's participation or compliance with the treatment.

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): NCT04782752


Contacts
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Contact: Marc de Perrot, MD, MSc 416 340-5549 marc.deperrot@uhn.ca
Contact: John Cho, MD, PhD 416-946-4501 ext 6513 John.Cho@rmp.uhn.ca

Locations
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Canada, Ontario
Toronto General Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Marc de Perrot, MD, MSc    416 340-5549    Marc.dePerrot@uhn.ca   
Contact: Fatemeh Zaeimi, MSc    416-340-5686    Fatemeh.Zaeimi@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04782752    
Other Study ID Numbers: 20-5902
First Posted: March 4, 2021    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No