Open-label, Multicenter, Randomized Phase II Trial of Treatment With Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients Affected by Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer With High Thymidylate Synthase Expression

NCT02919462 | Terminated Phase 2

• 2 other identifiers: IRST162.102015-003440-39
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open-label, multicentre, randomized phase II trial. Eligible patients with Non Small Cell Lung Cancer (NSCLC) with high Thymidylate Synthase (TS) expression , will be randomly assigned with 1:1 ratio to the following treatment Arms: A. 4 cycles of Cisplatin + Oral Vinorelbine followed by maintenance with Metronomic Oral Vinorelbine until disease progression B. 4 cycles of Cisplatin + Pemetrexed followed by maintenance with Pemetrexed until disease progression Treatment will be repeated every 21 days .

Conditions

Carcinoma, Non-Small-Cell Lung; Secondary; Advanced Stage IIIB; High Thymidylate Synthase Expression

Keywords

Carcinoma, Non-Small-Cell Lung; advanced stage IIIB; high Thymidylate Synthase expression; Treatment; Chemotherapy Naïve Patients; stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer; Cisplatin and Pemetrexed; Cisplatin and Oral Vinorelbine

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  Rate (DCR; complete response (CR) plus partial response (PR) plus stable disease (SD)). The response is assessed according to the RECIST 1.1 criteria.

  up to 36 months

Secondary Outcomes (4)

• Toxicity

  up to 36 months

• Overall survival (OS) within th 2 arms

  up to 36 months

• Progression free survival (PFS) within the two arms

  up to 36 months

• optimal TS H-score cutpoint

  up to 36 months

Study Arms (2)

Treatment Arm A

EXPERIMENTAL

Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles. Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).

Drug: Oral vinorelbine; Drug: Cisplatin; Drug: Maintenance with Metronomic Oral Vinorelbine

Treatment Arm B

ACTIVE COMPARATOR

Pemetrexed, 500 mg/m2, day 1 + Cisplatin, 75 mg/m2, day 1 every 3 weeks, for 4 cycles. Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks). 7-10 days before treatment administration, premedication with vitamin B12 1000µg intramuscular injection (every 9 weeks) and folate 1mg every day should be commenced.

Drug: Pemetrexed; Drug: Cisplatin; Drug: Maintenance with Pemetrexed

Interventions

Oral vinorelbine DRUG

Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) every 3 weeks, for 4 cycles

Treatment Arm A

Cisplatin DRUG

Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles

Treatment Arm A

Maintenance with Metronomic Oral Vinorelbine DRUG

Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).

Treatment Arm A

Pemetrexed DRUG

Pemetrexed, 500 mg/m2, day 1 every 3 weeks, for 4 cycles

Treatment Arm B

Maintenance with Pemetrexed DRUG

Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks)

Treatment Arm B

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically Non-squamous NSCLC, (including those with a non-specified tumor type).
• Metastatic (stage IV, both M1A or M1B) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes) according to TNM VII edition.
• TS nuclear H-score ≥ 70 or with TS nuclear and cytoplasmatic H-score ≥ 210.
• Patients at first diagnosis or those with disease recurrence after former surgery are eligible.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 9.2 and Appendix E for the evaluation of measurable disease.
• At least one target or non-target lesion not previously irradiated according to RECIST version 1.1
• Male or Female, aged ≥18 years.
• Life expectancy greater than 3 months.
• ECOG performance status ≤2 (see Appendix C).
• Patients must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/µL
• absolute neutrophil count ≥1,000µL
• platelets ≥100,000/µL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal

You may not qualify if:

• Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease.
• Prior surgery and/or localised irradiation is permitted if delivered outside to the target lesion.
• Prior adjuvant chemotherapy is permitted if it did not contain vinorelbine and pemetrexed and if administered at least 6 months prior entering the study.
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
• Patients with symptomatic brain metastasis or spinal cord compression that has not yet been treated with surgery and/or radiation. Patients with CNS metastases or spinal cord compression previously treated with surgery and/or radiation are eligible if they are asymptomatic and do not require escalating high dose steroids (anti-seizure medications are allowed)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed, vinorelbine, cisplatin, carboplatin or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix or surgically resected prostate cancer with normal PSA);
• NSCLC with EGFR mutation (or not able to use EGFR inhibitor) or with anaplastic lymphoma kinase (ALK) gene translocation (such as EML4-ALK).
• Has a known allergy, hypersensitivity, or contraindication to cisplatin, pemetrexed, or vinorelbine or any components used in their preparation or has a contraindication specified in section 7.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead
• Pierre Fabre Laboratories: collaborator

Study Sites (5)

Ircc Irst

Meldola, FC, 47014, Italy

Location

U.O. Oncologia Medica

Faenza, RA, 48018, Italy

Location

Claudio Dazzi

Ravenna, RA, 48121, Italy

Location

Ospedale di Piacenza, ASL Piacenza

Piacenza, Italy

Location

U.O. Oncologia Ospedale degli Infermi

Rimini, Italy

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Vinorelbine; Cisplatin; Maintenance; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Health Care Facilities Workforce and Services; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Claudio Dazzi, MD

  UOC Oncologia Medica - PO di Ravenna - AUSL della Romagna-RAVENNA Viale Randi 5 - 48121 Ravenna

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 28, 2016
• First Posted: September 29, 2016
• Study Start: March 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: January 16, 2018

Record last verified: 2018-01

Locations

IT (5)