| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| relapsed or refractory small cell lung cancer (SCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| small cell lung cancer that is unresponsive or no longer responding to previous treatment |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10041067 |
| E.1.2 | Term | Small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| to compare overall survival (OS) in subjects treated with dinutuximab and irinotecan versus subjects treated with irinotecan alone as a second-line treatment for relapsed or refractory small cell lung cancer (SCLC). |
|
| E.2.2 | Secondary objectives of the trial |
• To compare progression-free survival (PFS), objective response rate (ORR) (complete response [CR] + partial response [PR]) and clinical benefit rate (CR + PR + stable disease [SD]) in subjects treated with dinutuximab and irinotecan versus subjects treated with irinotecan alone.
• To compare the safety of subjects treated with dinutuximab and irinotecan versus subjects treated with irinotecan alone.
• To evaluate the pharmacokinetics of subjects treated with dinutuximab.
• To compare OS, PFS, ORR, and clinical benefit rate (CBR) in subjects treated with dinutuximab and irinotecan versus subjects treated with topotecan alone.
The exploratory objective of the study is to assess the relationship between selected biomarkers and survival of subjects treated with dinutuximab. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
3.1.1. Provide a signed informed consent form before any screening procedures.
3.1.2. Aged ≥18 years on the date of signing the informed consent form.
3.1.3. Have histologically or cytologically confirmed SCLC (undifferentiated small cell carcinoma arising in or consistent with lung cancer origin).
3.1.4. Documented (radiographic evidence of) relapse or disease progression during or after first-line platinum-based therapy (subjects refractory to initial platinum-based therapy are eligible).
3.1.5. No more than 1 prior regimen for SCLC. First-line platinum-based
therapy followed by maintenance therapy is considered a single regimen
provided there is no intervening disease progression.
3.1.6. Have no curative therapy available.
3.1.7. Have a life expectancy of at least 12 weeks.
3.1.8. Have Eastern Cooperative Oncology Group (ECOG) performance
status of 0 or 1.
3.1.9. Have adequate bone marrow function as assessed by the following
laboratory test results:
− Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (erythropoietin or transfusion
permitted).
− Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L
(growth factors permitted).
− Platelet count ≥100,000/mm3 or ≥100 x 109/L (transfusions or
thrombopoietic growth factors permitted).
3.1.10. Have calculated creatinine clearance (CrCL) ≥30 mL/minute
(using Cockcroft and Gault's formula) or serum creatinine ≤1.5 times
below the ULN.
3.1.11. Have adequate hepatic function, as assessed by the following
laboratory test results:
− Total bilirubin ≤1.5 times the ULN. (Subjects with Gilbert's Syndrome
or other benign congenital hyperbilirubinemia may be eligible at the
investigator's discretion in consultation with the Medical Monitor.
− Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤3.0 times ULN in subjects without liver metastases or ≤5.0 times ULN in
subjects with liver metastases.
3.1.12. Women of reproductive potential must have a negative urine or
serum beta human chorionic gonadotropin (β-HCG) pregnancy test
obtained within 7 days prior to the first dose of study treatment
(dinutuximab and/or chemotherapy)
− Women not of reproductive potential are female subjects who are
postmenopausal or permanently sterilized (e.g. tubal occlusion,
hysterectomy, bilateral salpingectomy).
3.1.13. Women of reproductive potential must agree to consistently use
one form of highly effective contraception plus one additional form of
contraception simultaneously or to practice complete abstinence from
vaginal intercourse. The requirement for two forms of contraception or
complete abstinence from vaginal intercourse applies from the time of
informed consent until 90 days following the last dose of all study drugs.
Male subjects who are sexually active with a female of reproductive
potential must agree to use a condom from the time of informed consent
until 90 days following the last dose of all study drugs.
The following are examples of highly effective and additional methods of contraception:
Highly effective methods (must use one):
• Hormonal associated with inhibition of ovulation (oral, injectable,
implantable, intravaginal, transdermal)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Tubal ligation
• Vasectomy for partner
Additional effective methods (must use one):
• Male or female condom with or without spermicide
• Cap, diaphragm or sponge with spermicide
• Combination of male condom with either cap, diaphragm or sponge
with spermicide (double barrier methods) |
|
| E.4 | Principal exclusion criteria |
3.2.1. Candidate for re-treatment with original platinum-based regimen
as second-line therapy.
3.2.2. Prior treatment with irinotecan, topotecan or dinutuximab.
3.2.3. Have active brain metastases. Subjects with brain metastases are
allowed if they completed definitive brain therapy, are asymptomatic and
radiologically stable, and if they are not currently receiving
corticosteroids or radiation. Subjects in whom steroids are being tapered
may be eligible with prior approval of the Medical Monitor.
3.2.4. Have mixed small-cell and non-small-cell histologic features.
3.2.5. Have a previous or concurrent cancer that is distinct in primary
site or histology from the cancer being evaluated in this study, except
cervical carcinoma in situ, treated basal cell carcinoma, superficial
bladder tumors (Ta and Tis [carcinoma in situ]) or any previous cancer
curatively treated <3 years ago.
3.2.6. Have a history or current evidence of uncontrolled cardiovascular
disease including but not limited to the following conditions:
− Congestive heart failure of New York Heart Association (NYHA) grade
3 or greater.
− Unstable angina (symptoms of angina at rest) or new-onset angina
within 6 months.
− Arterial thrombosis, deep vein thrombosis, or pulmonary embolism
within 6 months.
− Myocardial infarction or stroke within 6 months.
− Pericarditis (any CTCAE v.4.03 grade), pericardial effusion (CTCAE
v4.03 Grade ≥2).
3.2.7. Have a history of atypical thrombotic thrombocytopenic purpura
(TTP) or hemolytic uremic syndrome (HUS).
3.2.8. Women who are pregnant or breast-feeding.
3.2.9. Have not recovered from prior surgery, significant trauma,
systemic anticancer therapy (e.g., chemotherapy, biologic therapy,
immunotherapy), radiation therapy or investigational therapy to Grade 1
or better toxicity prior to enrollment (Part 1) or randomization (Part 2).
3.2.10. Have had organ allograft or hematopoietic transplantation.
3.2.11. Known to be human immunodeficiency virus (HIV) positive.
3.2.12. Have an active infection requiring treatment or one that is
clinically serious in the Investigator's opinion.
3.2.13. Have received a live vaccine within 6 months of enrollment (Part
1) or randomization (Part 2).
3.2.14. Exposure to strong CYP3A4 and/or UGT1A1 inhibitors and strong
CYP3A4 inducers within 14 days of enrollment (Part 1) or randomization
(Part 2).
3.2.15. Have any clinical condition that is considered unstable or might
jeopardize the safety of the subject and / or influence the subject's
compliance in the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is overall survival (OS)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints will be tested in the following sequence:
• PFS
• ORR
• CBR |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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) | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 98 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Bulgaria |
| Canada |
| France |
| Georgia |
| Germany |
| Hong Kong |
| Hungary |
| Italy |
| Korea, Republic of |
| Lithuania |
| Malaysia |
| New Zealand |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Thailand |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
| Last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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