Combination of Platinum Doublets and Hypofractionated Radiotherapy in NSCLC

Non-Small Cell Lung Cancer Clinical Trial

— HYPOLAN  

Official title:

Feasibility Trial on Combination of Platinum Doublets and Hypofractionated Radiotherapy for Locally-advanced Stage and / or Inoperable Non-small Cell Lung Carcinoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02947113
• Other study ID #: N16HYP
• Secondary ID: 2016-003790-18NL
• Status: Withdrawn
• Phase: Phase 2
• First received: October 14, 2016
• Last updated: November 28, 2017
• Start date: November 2017
• Est. completion date: November 2017

Study information

• Verified date: November 2017
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung carcinoma (NSCLC). Different chemotherapy and radiation regimens have been advocated but in general, cisplatin-doublets are deemed standard of care. Decreasing the overall treatment time of irradiation by hypofractionation is thought to increase the efficacy. Extensive experience is available on the combination of daily-dose cisplatin in combination with hypofractionated radiotherapy. However, no data is available on the safety of cisplatin doublets and hypofractionated radiotherapy

Description:

Patients presenting with locally advanced NSCLC will be consented to participate in this phase 2 trial that evaluates the concurrent treatment of cisplatin (Day 1: 75mg/m2) and pemetrexed (Day 1: 500mg/m2 for non-squamous cell lung cancer) or etoposide (Day1-3 100mg/m2 for squamous cell lung cancer), 3-weekly regimens, together with radiotherapy (24 daily fractions of 2.42 Gy to the mediastinal lymph nodes with an integrated boost of 2.75 Gy to the primary tumour). An interim analysis is planned following the first cohort of 25 patients to assess safety.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provision of signed, written and dated informed consent prior to any study specific procedures

• Male or female aged 18 years or older

• Cytological or histological proven NSCLC stage III or inoperable stage II (cT1-3-3N0-1), according to the 8th edition of the AJCC staging.

• Patients with locoregional recurrent lung tumor following surgery or a second primary cancer are eligible, unless a pneumonectomy was performed.

• Minimum required laboratory data

• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) =1.5 x 109/L, platelets = 100 x 109/L, and hemoglobin = 5.5 mmol/L.

• Hepatic:

i. Serum bilirubin = 1.5 times the upper limit of normal (× ULN); alkaline phosphatase (AP), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) = 3.0 × ULN.

ii. This does not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) who will be allowed in consultation with their physician.

• Renal: GFR = 60 ml/min; if below this threshold a creatinine clearance (CrCL) can be calculated based on the original weight based Cockcroft and Gault formula and should be = 45 ml/min.

Exclusion Criteria:

• WHO performance status = 2

• FEV-1 and DLCO < 35 % of the age- and gender adjusted normal value

• Patients with grade 3 dyspnea or worse at baseline (according to CTCAE version 4.03)

• Prior radiotherapy to the thorax.

• Mean lung dose > 20.0 Gy and/or exceeding other organs-at-risk constraints (page 21).

• Participation in another clinical study with an investigational product during the last 4 weeks.

• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study

• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of chemotherapy.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent

• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control

• Any condition that, in the opinion of the investigator, would interfere with evaluation of the chemoradiotherapy or interpretation of patient safety or study results.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Cisplatin
Cisplatin will be administrated in a 3-weekly scheme for 2 courses combined with pemetrexed (non-squamous cell lung cancer) or etoposide (squamous cell lung cancer)

Radiation:
• hypofractionated radiotherapy
Hypofractionated radiotherapy of 24 x 2.75 Gy will be given combined with a 3-weekly scheme of cisplatin and pemetrexed/etoposide

Drug:
• Pemetrexed
Pemetrexed will be administrated in a combination with cisplatin and hypofractionated radiotherapy (for non-squamous cell lung cancer)
• Etoposide
etoposide will be administrated in a combination with cisplatin and hypofractionated radiotherapy (for squamous cell lung cancer)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

References & Publications (3)

Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. doi: 10.1093/jnci/djr325. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012 Jan 4;104(1):79. — View Citation

Kwint M, Uyterlinde W, Nijkamp J, Chen C, de Bois J, Sonke JJ, van den Heuvel M, Knegjens J, van Herk M, Belderbos J. Acute esophagus toxicity in lung cancer patients after intensity modulated radiation therapy and concurrent chemotherapy. Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):e223-8. doi: 10.1016/j.ijrobp.2012.03.027. Epub 2012 May 5. — View Citation

Mauguen A, Le Péchoux C, Saunders MI, Schild SE, Turrisi AT, Baumann M, Sause WT, Ball D, Belani CP, Bonner JA, Zajusz A, Dahlberg SE, Nankivell M, Mandrekar SJ, Paulus R, Behrendt K, Koch R, Bishop JF, Dische S, Arriagada R, De Ruysscher D, Pignon JP. Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol. 2012 Aug 1;30(22):2788-97. doi: 10.1200/JCO.2012.41.6677. Epub 2012 Jul 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	biomarker	assessment of circulating cell free tumor DNA for residual disease	through study completion, an average of 2 years
Primary	Incidence of treatment related Adverse events (according to CTCAE v 4.03)	safety defined by the rate of grade 3-5 adverse events	within 3 months FU
Secondary	safety defined by the rate of grade 3-4 treatment related adverse events	safety will be assessed by the incidence of grade 3-4 related adverse event (CTCAE v 4.03)	3 months
Secondary	disease control rate		1 year
Secondary	progression free survival		2 years
Secondary	overall survival		2 years