Efficacy and Safety of CRT, Durvalumab and Surgery for SST

NCT04465968 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: JCOG1807C
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

Brief Summary

The safety and efficacy of multimodality treatment of pre- and post-operative durvalumab therapy after pre-operative chemoradiotherapy for resectable superior sulcus tumor (SST) and durvalumab maintenance therapy after chemoradiotherapy for unresectable SST

Conditions

Superior Sulcus Tumor; Non-small Cell Lung Cancer Stage IIB; Non Small Cell Lung Cancer Stage III

Keywords

Superior Sulcus Tumor; Pancoast Tumor; Non-Small Cell Lung Cancer; Durvalumab; Multi-modality therapy; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• 3-year overall survival rate (3y-OS)

  3-year overall survival rate

  3 years

Secondary Outcomes (15)

• 3-year progression-free survival rate (3y-PFS)

  3 years

• 5-year progression-free survival rate (5y-PFS)

  5 years

• 5-year overall survival rate (5y-OS)

  5 years

• Mode of recurrence

  5 years

• Local recurrence rate

  5 years

Study Arms (1)

CRT + Durvalumab ± Surgery + Durvalumab

EXPERIMENTAL

Concurrent chemoradiotherapy (cisplatin+S-1+radiotherapy 66Gy)+2 courses of durvalumab followed by Surgery and adjuvant durvalumab for resectable SST or chemoradiotherapy (cisplatin+S-1+radiotherapy 66Gy) followed by maintenance durvalumab for unresectable SST.

Drug: Cisplatin; Drug: S1; Radiation: concurrent radiotherapy; Drug: Durvalumab; Procedure: Surgery

Interventions

Cisplatin DRUG

Cisplatin 60 mg/m2, IV, day 1

CRT + Durvalumab ± Surgery + Durvalumab

S1 DRUG

80 - 120 mg/day, PO, day 1-14

CRT + Durvalumab ± Surgery + Durvalumab

concurrent radiotherapy RADIATION

66 Gy/33 Fr

CRT + Durvalumab ± Surgery + Durvalumab

Durvalumab DRUG

preoperative durvalumab therapy within 28 days after chemoradiotherapy. Two courses are given every two weeks.

CRT + Durvalumab ± Surgery + Durvalumab

Surgery PROCEDURE

Surgery will be performed between day 15 and day 42 of the second course of preoperative durvalumab therapy after confirming that all surgical operation criteria are met.

CRT + Durvalumab ± Surgery + Durvalumab

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A definite diagnosis of non-small cell lung cancer has been obtained by biopsy from the primary lesion.
• Meet all of the following (UICC-TNM classification 8th edition). I. Regarding the primary lesion, meet one of the following on chest CT. i. Direct invasion of the chest wall at or above the height of the first rib (at least invasion of the parietal pleura) ii. Direct invasion of the subclavian artery or vein II. Regarding regional lymph nodes, meet either of the following by chest CT and FDG-PET/CT. Metastasis is also considered if lymph node metastasis is determined by either chest CT or FDG-PET/CT.
• i. cN0 ii. cN1 and no metastases to #10, #11, and #12 lymph nodes iii. cN3 (ipsilateral supraclavicular lymph node metastasis) and no metastases in regional lymph nodes (N1 and N2) other than "#13, #14 lymph nodes" III. No distant metastases (including intrapulmonary metastases in the same ling lobe and in a different lung lobe on the same side) on imaging tests including FDG-PET/CT
• It is judged that radical resection is possible by lobectomy (including bilobectomy for 2 lobes), which satisfies the following \[1\] and \[2\].
• I. The board respiratory surgeon judges that none of the following is true based on the image findings.
• i. There is vertebral body infiltration that requires total spondylectomy ii. Presence of spinal cord infiltration iii. Invaded trachea or tracheal bifurcation iv. Invasion of aortic arch or ascending aorta v. Invading brachial plexus at C8 or higher vi. Esophageal infiltration that requires esophageal reconstruction for resection vii. Pneumonectomy is required for radical resection II. Meet all of the following. i. Predicted postoperative forced expiratory volume of 1 second (FEV1.0) ≥ 800 mL within 56 days before registration ii. SpO2 \> 93% (room air) with the latest inspection value within 14 days before registration
• Consult with the radiotherapy doctor and it is judged that all of the following are met.
• I. Radiation therapy is possible according to the protocol II. The irradiation field does not reach the hilum
• The age of the registration date is 20 years or older and 75 years or yonger.
• Performance status (PS) is 0 or 1 according to ECOG standards (PS must be described in medical records)
• The presence or absence of measurable lesions is not required.
• No history of following surgery irrespective of whether for a benign or malignant lesion.
• I. Thoracoscopic surgery or thoracotomy with excision of the affected lung or esophagus or mediastinum (however, a history of thoracoscopic surgery without wedge resection or lung, esophagus, or mediastinal resection (eg, pleural biopsy)) is allowed) II. Median sternotomy surgery (with or without organ resection) III. Pulmonary resection other than wedge resection of the contralateral lung (whether open-heart surgery or thoracoscopic surgery)
• There is no history of chemotherapy, including treatment for other cancer types (including molecular targeted therapies and immune checkpoint inhibitors). However, the history of drug therapy as adjuvant therapy is allowed if it was completed more than 3 years ago. In addition, a history of hormone therapy for other cancer types is allowed.
• If there is a history of radiotherapy including other cancer types, the lung, hilum, mediastinum, and supraclavicular fossa are not included in the irradiation field.

You may not qualify if:

• Having active double cancer (simultaneous double cancer/multiple cancer and metachronous double cancer/multiple cancer with a disease-free period of 3 years or less, even if the disease-free period is less than 3 years, clinical The 5-year relative survival rate is similar to that of stage I prostate cancer, clinical stage 0 completely responded to radiation therapy, stage I laryngeal cancer, and complete excision of the following pathological stage cancers. History of cancer equivalent to 95% or more is not included in active double cancer/multiple cancer). Gastric cancer "adenocarcinoma (general type)": Stage 0-I, colon cancer (adenocarcinoma): Stage 0-I, rectal cancer (adenocarcinoma): Stage 0-I, esophageal cancer (squamous cell carcinoma, glandular) Squamous cell carcinoma, basal cell carcinoma): Stage 0, breast cancer (non-invasive ductal carcinoma, lobular carcinoma): Stage 0, breast cancer (invasive ductal carcinoma, lobular invasive carcinoma, Paget's disease): 0 Stage-IIA, endometrial cancer (endometrioid adenocarcinoma, mucinous adenocarcinoma): Stage I, prostate cancer (adenocarcinoma): Stage I-II, cervical cancer (squamous cell carcinoma): Stage 0, thyroid cancer (Papillary cancer, follicular cancer): stage I, stage II, stage III, renal cancer (clear cell carcinoma, chromophobe cell carcinoma): stage I, non-melanoma skin cancer, malignant melanoma without a definite diagnosis, etc. Lesions of intramucosal cancer
• Has an infectious disease that requires systemic treatment (including active pulmonary tuberculosis).
• When registering, a fever of 38.0°C or higher is generated.
• Women who are pregnant, possibly pregnant, within 28 days of delivery, or breastfeeding. A man who wants a partner to become pregnant. Or a reproductive male or female patient who is not willing to use an effective contraceptive by Week 13 (Day 91) after the last dose of durvalumab (see 6.4.7.).
• Participation in the study is considered to be difficult due to the combination of mental illnesses or symptoms that impair daily life.
• Continuous systemic administration (oral or intravenous) of steroid drugs or other immunosuppressive drugs in excess of 10 mg/day in terms of prednisolone.
• With uncontrolled diabetes.
• With uncontrolled hypertension.
• A gastrointestinal disorder accompanied by uncontrolled diarrhea.
• With unstable angina (angina with onset or exacerbation of attack within the last 3 weeks) or a history of myocardial infarction within 6 months.
• Poor valvular heart disease, dilated cardiomyopathy, hypertrophic cardiomyopathy, congestive heart failure, and arrhythmia.
• Chest CT reveals severe emphysema.
• Either HBs antigen, HCV antibody, or HIV1/2 antibody is positive.
• Continuous use of flucytosine (Ancotil®) is required.
• Participating in another clinical trial (excluding observational studies) during the 6 months prior to enrollment.

Sponsors & Collaborators

• National Cancer Center Hospital East: lead
• AstraZeneca: collaborator
• Japan Agency for Medical Research and Development: collaborator
• Japan Clinical Oncology Group: collaborator

MeSH Terms

Conditions

Pancoast Syndrome; Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; S 1 (combination); durvalumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Masahiro Tsuboi, MD

CONTACT

+81-4-7133-1111; mtsuboi@east.ncc.go.jp

Keiju Aokage, MD

CONTACT

+81-4-7133-1111; kaokage@east.ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 10, 2020
• Study Start: September 1, 2020
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2030
• Last Updated: July 10, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share