Combination of Platinum Doublets and Hypofractionated Radiotherapy in NSCLC

NCT02947113 | Withdrawn Phase 2

• 3 other identifiers: N16HYP2016-003790-18NL57625.031.16
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Non-Small Cell Lung Cancer

Keywords

cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• safety defined by the rate of grade 3-4 treatment related adverse events

  3 months

• disease control rate

  1 year

• progression free survival

  2 years

• overall survival

  2 years

Other Outcomes (1)

• biomarker

  through study completion, an average of 2 years

Study Arms (1)

chemotherapy combined with radiotherapy

EXPERIMENTAL

Patients will be treated with two 3-weekly courses of cisplatin (Day 1: 75mg/m2) and pemetrexed (Day 1: 500mg/m2 for non-squamous) or etoposide (Day1-3 100mg/m2 for squamous), together with hypofractionated radiotherapy (24 daily fractions of 2.42 Gy to the involved mediastinal lymph nodes with an integrated boost of 2.75 Gy to the primary tumor).

Drug: Cisplatin; Radiation: hypofractionated radiotherapy; Drug: Pemetrexed; Drug: Etoposide

Interventions

Cisplatin DRUG

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)

chemotherapy combined with radiotherapy

hypofractionated radiotherapy RADIATION

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

chemotherapy combined with radiotherapy

Pemetrexed DRUG

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

Also known as: Alimta

chemotherapy combined with radiotherapy

Etoposide DRUG

etoposide will be administrated in a combination with cisplatin and hypofractionated radiotherapy (for squamous cell lung cancer)

Also known as: Etoposin

chemotherapy combined with radiotherapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Related 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.

  PMID: 21903745 BACKGROUND

• 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.

  PMID: 22560551 BACKGROUND

• Mauguen A, Le Pechoux 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.

  PMID: 22753901 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Cisplatin; Radiation Dose Hypofractionation; Pemetrexed; Etoposide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Judi van Diessen, MD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: October 27, 2016
• Study Start: November 1, 2017
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: November 30, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share