Mitigation of Radiation Pneumonitis, Fibrosis and Heart Toxicity With Nicorandil in Lung Cancer Patients

Radiation Pneumonitis Clinical Trial

Official title:

Mitigation of Radiation Pneumonitis, Fibrosis and Heart Toxicity With Nicorandil in Lung Cancer Patients

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02809456
• Other study ID #: N201508038
• Status: Enrolling by invitation
• Phase: Phase 2
• First received: June 9, 2016
• Last updated: June 22, 2016
• Start date: July 2016
• Est. completion date: December 2019

Study information

• Verified date: June 2016
• Source: Taipei Medical University WanFang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taipei Medical University: Taiwan, R.O.C
• Study type: Interventional

Clinical Trial Summary

This project will test the effect of nicorandil to mitigate the lung damage that can occur as a side effect of radiation therapy for lung cancer. Thousands of veterans develop lung cancer every year, and are treated by radiation therapy. Studies of lung radiation injury in laboratory animals show that with nicorandil, investigators can significantly reduce the severity of lung fibrosis and heart toxicity.1,2 Nicorandil is FDA approved and in common use for treatment of angina. These studies will advance that work to human use. Successful mitigation of lung radiation damage and heart toxicity will improve the quality of life in veterans and non-veterans who are treated for lung cancer by radiation, and may also improve cure rates of radiation therapy for lung cancer.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 50
• Est. completion date: December 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Histologically or cytologically-proven NSCLC; mixed histology with small cell lung carcinoma (SCLC) component not allowed

2. Patients with stage II - IV NSCLC who received at least 54 Gy of total planned thoracic radiation dose will be eligible; patients must have received at least one cycle of chemotherapy concurrently during the course of thoracic radiation; regimens allowed are platinum combinations with either etoposide or a taxane regardless of histology subtype; platinum with pemetrexed for patients with nonsquamous NSCLC only; patients with oligometastatic stage IV cancer are eligible if they have received only one line of systemic therapy for their stage IV cancer prior to the concurrent chemoradiation phase

3. Patient must have had a CR/PR/SD, 4-6 weeks after completing last fraction of chemotherapy / radiation therapy.

4. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 at the time of randomization

5. Absolute neutrophil count (ANC) >= 1,500/uL

6. Platelet count >= 100,000/uL

7. Hemoglobin >= 9 g/dL

8. Total bilirubin =< 1.5 times upper limit of normal (ULN) OR direct bilirubin normal (per institute standards)

9. Aspartate aminotransferase (AST) =< 1.5 x ULN; alanine aminotransferase (ALT) and AST =< 3 x ULN is acceptable if there is liver metastasis

10. Fertile patients must use adequate contraception

Exclusion Criteria:

1. Whole-brain radiotherapy (WBRT) < 14 days from the anticipated start of nicorandil/placebo administration

2. Unable to start nicorandil/placebo treatment between 4 - 6 weeks after completing the last dose of thoracic radiation

3. Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks; dexamethasone allowed if total daily dose does not exceed 2 mg

4. Major injuries or surgery (e.g., craniotomy) < 28 days from the start of nicorandil/placebo administration; wound should be healed prior to starting therapy

5. Second malignancies are allowed as long as the disease does not require active treatment with concomitant systemic cytotoxic chemotherapy, investigational or biologic therapy (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] or human epidermal growth factor receptor 2 [HER2] monoclonal antibodies); hormone-related therapies (e.g., gonadotrophin releasing hormone (LHRH) agonists, tamoxifen, etc.) are allowed

6. Concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would increase the risk associated with study participation and/or limit compliance with study requirements

7. Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher proteinuria

8. Systemic therapy or investigational agent administered < 28 days prior to treatment with nicorandil

9. Pregnancy or breast feeding; female patients with child-bearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin [B-HCG] test in urine or serum) prior to commencing study treatment

10. Creatinine > 1.5 x ULN or creatinine clearance levels (CrCL) < 45 mL/min

11. Centrally located tumors with radiographic evidence (computed tomography [CT] or magnetic resonance imaging [MRI]) of local invasion of major blood vessels

12. acute myocardial infarction within 2 weeks before percutaneous coronary intervention

13. contraindications to treatment with nicorandil (allergy, glaucoma, digestive ulcer, is currently taking phosphodiesterase-5 inhibitor)

14. bypass restenosis

15. PCI history

16. hypotension

17. impaired liver function

18. renal insufficiency requiring hemodialysis

19. pregnancy

20. connective tissue disease

21. life expectancy = 12 months

22. left main coronary artery disease

23. bypass graft lesion and lesions unsuitable for OCT

24. unwillingness or inability to provide informed consent

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pneumonia
• Radiation Pneumonitis

Intervention

Drug:
• Nicorandil
oral intake

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Medical University WanFang Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of symptomatic radiation pneumonitis in patients with unresectable Stage II/III/ oligometastatic IV non-small cell lung carcinoma (NSCLC) who completed chemoradiation followed by nicorandil or not		Up to 2.5 years post-treatment	Yes
Secondary	The quality of life (QOL) questionnaire		Baseline up to 2.5 years post-treatment	Yes
Secondary	Biomarker analysis such as TGF-ß, Serum surfactant proteins-A & -D, MMP1 and MMP7		Up to 97 days post-treatment	Yes
Secondary	The overall survival in patients who received nicorandil versus observation		Up to 2.5 years post-treatment	Yes
Secondary	Radiation pneumonitis (RP) score in patients who received nicorandil versus observation		Baseline up to 2.5 years post-treatment	Yes
Secondary	The composite index (based on PFT, RP score and QOL) at the end of active treatment and 6 months after completion of treatment between patients who received nicorandil versus observation.		Baseline up to 2.5 years post-treatment	Yes
Secondary	Responses rates		Up to 2.5 years post-treatment	Yes