Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05269485 |
| Other study ID # |
ky270 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2022 |
| Est. completion date |
June 1, 2023 |
Study information
| Verified date |
March 2022 |
| Source |
Anhui Provincial Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Definitive concurrent chemoradiotherapy followed by durvalumab (Pacific protocol) has been
the standard modality for stage III locally advanced non-small cell lung cancer. In spite of
the median overall survival of 47.5 months, there still existed 38.5% and 6.9% patients who
finally developed intra-thorax and extra-thorax recurrence respectively in long-term
follow-up. The relatively low local control rate has been the bottleneck for further
improvement of overall survival. Hypofraction radiotherapy has been validated to be able to
increase the local control rate in two prospective trials. Therefore, this trial is designed
to explore the safety and primary efficacy of hypofraction radiotherapy followed by immune
checkpoint inhibitors for stage III locally advanced non-small cell lung cancer.
Description:
Trial title: Hypofraction radiotherapy followed by immune checkpoint inhibitors for locally
advanced non-small cell lung cancer: A phase I/II clinical trial.
Trial objective: To explore the safety and primary efficacy of hypofraction radiotherapy
followed by immune checkpoint inhibitors for stage III locally advanced non-small cell lung
cancer.
Trial Design: To enroll 36 patients diagnosed with stage III locally advanced non-small cell
lung cancer to receive hypofraction radiotherapy (18 patients receiving high dose of 60-68
(Gray, Gy) /15-17 (fraction, f) and 18 patients receiving low dose of 48Gy/12f) followed by
1-year maintenance of immune checkpoint inhibitors.
Inclusion Criteria: a. 18-70 years old; b. Eastern Cooperative Oncology Group (ECOG) 0-1; c.
non-small cell lung cancer including squamous cell carcinoma, adenocarcinoma, adenosquamous
carcinoma, large-cell carcinoma; d. wild-type of driven genes; e. stage III (AJCC 8th
Edition) confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone scan or cranial
MRI and Positron Emission Tomography (PET-CT); f. surgically unresectable or deny of surgery;
g. signature of inform consent.
Exclusion Criteria: a. younger than 18 years old or older than 70 years old; b. ECOG>1; c.
small-cell lung cancer and other neuroendocrine carcinoma including typical or atypical
carcinoid, large-cell neuroendocrine carcinoma; d. mutant type of driven genes; e. non stage
III (AJCC 8th Edition) confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone
scan or cranial MRI and PET-CT; f. surgically resectable; g. no signature of inform consent.
Staging Examination before Radiotherapy: a. ECOG scoring. b. Cranial contrast MRI and PET-CT,
or cranial contrast MRI (preferred), chest contrast CT, abdominal ultrasonography and bone
scan. c. Bronchoscopy for centrally-located lung cancer. d. Staging examination is mandatory
after inductive chemotherapy & chemotherapy with immunotherapy. e. Pulmonary function test.
Inductive therapy before radiotherapy: Chemotherapy or chemotherapy combined with
immunotherapy is allowed as inductive therapy. Detailed regimen could refer to NCCN
guidelines. Tyrosine kinase inhibitors are not allowed as inductive therapy.
Randomization: Patients would be randomly assigned to high dose group and low dose group
using random number table method.
Radiotherapy CT simulation: 4-Dimensional CT (4D-CT) with intravenous contrast is recommended
for simulation. Scan thickness should be less than 5 mm. Thermal mask or vacuum bag is
recommended.
Target Delineation: Considering hypofraction and involved field irradiation (IFI), only
Internal Tumor Volume (ITV) should be delineated without the need to delineate Clinical Tumor
Volume (CTV).
Delineation of ITV: ITV should include pulmonary gross tumor and metastatic mediastinal lymph
nodes. PET-CT registration with simulation CT is recommended for patients with obstructive
atelectasis. For patients with suspected mediastinal lymph nodes, Endobronchial
Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) is recommended.
Production of Planning Tumor Volume (PTV):
Low Dose Hypofraction Arm (48Gy/12f) PTV: PTV is produced by a margin of 5 mm added to ITV.
Modification of PTV is suggested to respect anatomic boundary.
High Dose Hypofraction Arm (60-68Gy/15-17f) PTV: Planning Tumor Volume (PTV) is produced by a
margin of 5 mm added to ITV. Modification of PTV is suggested to respect anatomic boundary.
For patients with ITV abutting esophagus, the technique of Esophagus-Sparing Simultaneous
Integrated Boost (ES-SIB) should be utilized. PTV should be modified not to cover esophagus
to ensure that the maximum dose to esophagus should be ≤ 45Gy. The dose to PTV in adjacent to
esophagus could be compromised (D99% of PTV should be ≥ 51Gy).
Dosimetric Limitation: 95% prescription dose should cover 100% PTV and 95% PTV should receive
100% prescription dose. Total Lung: V20<25%, Dmean<13Gy, V5<50%. Spinal Cord: Dmax<40Gy.
Heart: V30<40%, Dmean<25Gy.
Treatment Implementation: Radiotherapy is implemented every day. Cone-beam CT should utilized
every day to minimize set-up error.
Concurrent Chemotherapy: If patients have received over 4 cycles of inductive chemotherapy
with or without immunotherapy, no concurrent chemotherapy is needed. If patients have
received less than 4 cycles of inductive chemotherapy with or without immunotherapy,
concurrent chemotherapy is needed to ensure 4 cycles of chemotherapy. Adenocarcinoma:
Pemetrexed combined with platinum is recommended. Squamous-cell lung cancer: Etoposide
combined with platinum is recommended. One month after completion of radiotherapy, chest CT
and abdominal ultrasonography should be undertaken. After exclusion of disease progression
and grade 2 or more radiation-induced pneumonitis, consolidative immunotherapy should be
started. Durvalumab maintenance for one year is recommended.
Follow-up: Patients should be follow-up every three months right after the completion of
radiotherapy to 3 years after radiotherapy. Then follow-up every half year is allowed to 5
years after radiotherapy. After 5 years, follow-up every year is appropriate. In follow-up,
chest CT and abdominal ultrasonography should be implemented. Cranial MRI should be performed
every half year for patients with adenocarcinoma. Bone scan should be undertaken every year
for all patients.
Primary Endpoint: Rate of radiation-induced pneumonitis, esophagitis, myelosuppression (CTCAE
V4.0).
Secondary Endpoint: 1-year local-regional control rate, 1-year progression-free survival
rate, 1-year overall survival rate (RECIST v1.1).
