E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Interventional phase II clinical trial incorporating a parallel control group of patients receiving no adjuvant immunotherapy. Patients with non small lung cell carcinoma (NSCLC) in stage III A and III B who had no radiochemotherapy before will be enrolled into the phase II clinical trial. The aim of the study is to show the efficacy of an adjuvant treatment with Hsp70-peptide TKD/IL-2 activated, autologous NK cells following completion of standard radiochemotherapy (Cisplatin/Vinorelbine). |
interventionelle, klinische Phase II Studie die neben dem Prüfarm einen Kontrollarm ohne adjuvante Immuntherapie beinhaltet. Eingeschlossen werden Patienten mit einem histologisch gesicherten Bronchialkarzinom (NSCLC) im lokal fortgeschrittenen Stadium (Stadien IIIA und IIIB) nach Abschluss einer Radiochemotherapie (60-66Gy/Vinorelbine+Cisplatin). Das Ziel der Studie ist die Effektivität einer adjuvanten Immuntherapie mit aktivierten NK-Zellen zu überprüfen. |
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E.1.1.1 | Medical condition in easily understood language |
Interventional phase II clinical Patients with non small lung cell carcinoma in stage III A and III B. |
interventionelle, klinische Phase II Studie Eingeschlossen werden Patienten mit einem histologisch gesicherten Bronchialkarzinom (Stadien IIIA und IIIB) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006427 |
E.1.2 | Term | Bronchial carcinoma stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to examine whether an adjuvant treatment with TKD/IL-2-activated, patient-derived NK cells following definitive RCT is feasible and effective. Comparison of progression-free survival between treatment and control group A control arm with standard radiochemotherapy (Cisplatin/Vinorelbine) is part of this study, because Pfister et al (2007) could demonstrate that lung cancer patients with an Hsp70 membrane expression had a poorer clinical outcome with respect to overall survival when compared to their Hsp70 membrane counterparts. Therefore, all historic data on overall survival of lung cancer patients are the result of a mixture of Hsp70 positive and negative patients and median overall survival of Hsp70 positive lung cancer patients is not known. |
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E.2.2 | Secondary objectives of the trial |
To evaluate response to the treatment, toxicity, quality of life (LCSS), increase of overall survival and to determine biological parameters such as NK cell activation. Safety will be assessed according to NCI-CTC criteria. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. First diagnose of histologically and/or cytologically proven and unresectable NSCLC with clinically stage III A and III B
2. Completion of radiochemotherapy no longer than 8 weeks ago
3. Progression free according to RECIST 1.1 criteria at the first assessment after completion of radiochemotherapy
4. Confirmed presence of Hsp70 on patient´s tumors
5. Female or male, age 18 to 75 years
6. ECOG Status ≤ 2
7. Neutrophil count ≥ 1.5 x 109/l after completion of radiochemotherapy
8. WBC ≥ 2.5 x 109/l after completion of radiochemotherapy
9. Haemoglobin >8g/l after completion of radiochemotherapy
10. Platelet count ≥ 100 x 109/l after completion of radiochemotherapy
11. Normal renal function (creatinine <150% ULN)
12. Normal liver function (Bilirubin <200% ULN; G-GT, GPT und GOT <250% ULN;)
13. Normal blood coagulation (PTT 25-40s)
14. Measurable disease according to irRC criteria
15. Female patients of childbearing potential must have negative pregnancy test performed during screening period (≤ 14 days before initiation of study drug dosing). Postmenopausal women must be amenorrheal for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and for 6 months following discontinuation of study drug.
16. Written (signed) Informed Consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment and to participate in the study
17. Ability to comply with study and follow-up procedures
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E.4 | Principal exclusion criteria |
1. Prior treatment with any other investigational drug within 4 weeks prior to first dose of study medication
2. Any severe heart disease or any severe concomitant disease (ECOG stage > 2)
3. NSCLC patients (stage IIIA/B) eligible for initial surgery with a confirmed consent of an interdiscipliary Tumorboard
4. Patients that show ALK positivity or an activating mutation of the EGFR-TK domain
5. Patients with locally advanced or metastastic non-small cell lung cancer other than predominantly squamous cell histology
6. Any disease (including psychotic disorders, drug abuse, active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding likely (in the investigator’s opinion) to affect the evaluation of the study or place the patient at risk whilst on treatment
7. Any serious infection or sepsis
8. Any active autoimmune disease
9. Any immunodeficiency syndrome
10. Surgery or immunotherapy within 4 weeks before study entry
11. Patients with known hypersensitivity to any of the administered substances should be excluded from the clinical trial
12. Patients with a positive HIV test should be excluded from the clinical trial as well as patients with positive Hepatitis A, B, C tests
13. Receipt of immunosuppressive drugs including high dose systemic corticosteroids within 3 weeks before study entry. Low dose corticosteroids as they are a common treatment option for patients suffering from COPD are not an exclusion criterium.
14. Radio-, cytostatic-, and immuno-therapy in parallel or within 4 weeks prior to study start
15. Women who are pregnant or breast feeding
16. Female patients of reproductive potential unwilling to practice a highly effective method of birth control
17. History of noncompliance with medical regimens
18. Patients unwilling to or unable to comply with the protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
- Progression free survival (PFS) |
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E.5.2 | Secondary end point(s) |
- Response, toxicity, Quality of life (LCSS), Patients overall survival and NK activation
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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November 2018 |
LPLV 05 2020 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |