SABR for T1-2a N1 NSCLC

NCT03321760 | Withdrawn Phase 2 DMC

• 2 other identifiers: IUSCC-06261707319235
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

Conventionally fractionated radiation therapy given over 6-7 weeks alone, sequentially, or concurrent with chemotherapy have produced poor outcomes in Stage II NSCLC in most series. Stereotactic ablative radiotherapy (SABR) has been shown to be very effective and is now standard of care for Stage 1 disease. There has been initially reluctance to utilize SABR for central lung tumors because of published reports that showed an excess of toxicity when SABR was utilized; however, newer data with less intense treatment regimens suggest safety in treatment of central lung disease. The safety and efficacy of SABR in treating hilar nodes or N1 disease currently is not known fully and will be evaluated in this study.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of dose-limiting toxicities (DLTs) during the run-in period

  Any event per CTCAE v.4 that occurs within 30 days from the start of SABR, and is possibly, probably or definitely related to treatment, and is related to a specific list of symptoms which are outlined in the protocol.

  30 days

Secondary Outcomes (4)

• Local control

  2 years

• Progression free survival

  2 years

• Overall survival

  5 years

• Rate of dose-limiting toxicities (DLTs) at one year

  1 year

Study Arms (4)

Run-In Dose 1

EXPERIMENTAL

10 Gy dose delivered to the primary tumor \& 10 Gy to the hilar (N1) node over 5 fractions

Radiation: Stereotactic Ablative Radiation Therapy (SABR)

Run-In Dose -1

EXPERIMENTAL

10 Gy dose delivered to the primary tumor \& 9 Gy to the hilar (N1) node over 5 fractions

Radiation: Stereotactic Ablative Radiation Therapy (SABR)

Run-In Dose -2

EXPERIMENTAL

10 Gy dose delivered to the primary tumor \& 8 Gy to the hilar (N1) node over 5 fractions

Radiation: Stereotactic Ablative Radiation Therapy (SABR)

Phase 2

EXPERIMENTAL

The maximum tolerated radiation dose to the hilar (N1) node from the run-in period will be used during Phase 2.

Radiation: Stereotactic Ablative Radiation Therapy (SABR)

Interventions

Stereotactic Ablative Radiation Therapy (SABR) RADIATION

SABR will be delivered to the primary disease and hilar (N1) node over 5 fractions.Reductions may be made to the hilar (N1) node according to a 3+3 design during the run-in period.

Phase 2; Run-In Dose -1; Run-In Dose -2; Run-In Dose 1

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old at time of consent
• Ability to provide written informed consent and HIPAA authorization
• Pathological diagnosis of NSCLC lung cancer
• Staging PET/CT within 45 days of consult
• EBUS or other histologic confirmation of N1 involvement (diagnosis of lung cancer should come from the hilar \[N1\] disease)
• T1/2a \<5cm lung primary
• N1 disease \<5cm
• Patient refuses surgery or deemed inoperable
• KPS of \> 60
• Baseline labs including CBC/differential and BMP within 45 days of consult
• CBC/differential with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
• Adequate renal function defined as serum creatinine within normal institutional limits or creatinine clearance must be at least 20 ml/min

You may not qualify if:

• Previous radiation therapy overlapping with current radiation target as determined by the discretion of the investigator
• Inability to comply with treatment per investigator discretion.
• Inability to follow standard of care follow up recommendations per investigator discretion.
• Pregnant and breastfeeding women
• Contra-indication to platinum-based two drug chemotherapy as determined by the treating medical oncologist
• Patients with a history of chronic kidney disease or lactic acidosis
• Severe, active co-morbidity, defined as follows:
• i. Uncontrolled neuropathy ≥ grade 2 regardless of cause ii. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months iii. Transmural myocardial infarction within the last 6 months iv. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration v. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration vi. Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease vii. HIV positive with CD4 count \< 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
• viii. End-stage renal disease (i.e. on dialysis or dialysis has been recommended).

Sponsors & Collaborators

• Indiana University: lead
• Indiana University School of Medicine: collaborator

Study Sites (3)

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Tim Lautenschlaeger, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Model Details: This is a Phase II single-institution trial with a 3 + 3 safety run-in period. SABR will be delivered per protocol, followed by a planned 4 cycles of sequential chemotherapy within 3-8 weeks after the completion of SABR. Four cycles of chemotherapy shall be planned as typically used for adjuvant chemotherapy following surgical resection for T1-2aN1 non-small cell lung carcinoma (NSCLC) unless otherwise indicated by institutional guidelines.

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: October 26, 2017
• Study Start: January 1, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 9, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)