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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03098030




Registration number
NCT03098030
Ethics application status
Date submitted
22/03/2017
Date registered
31/03/2017
Date last updated
29/04/2020

Titles & IDs
Public title
Dinutuximab and Irinotecan Versus Irinotecan to Treat Subjects With Relapsed or Refractory Small Cell Lung Cancer
Scientific title
A Two-part, Open-label, Randomized, Phase 2/3 Study of Dinutuximab and Irinotecan Versus Irinotecan for Second Line Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer
Secondary ID [1] 0 0
DIV-SCLC-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Dinutuximab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Topotecan

Experimental: Part 1: Dinutuximab + Irinotecan - Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of every 21 days (q21d). Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 (and without opioids) and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV.

Active Comparator: Part 2: Irinotecan - Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle.

Experimental: Part 2: Dinutuximab + Irinotecan - Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 (and without opioids) and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV.

Active Comparator: Part 2: Topotecan - Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle.


Other interventions: Dinutuximab
Dinutuximab injection, for intravenous (IV) use

Treatment: Drugs: Irinotecan
Irinotecan injection, IV infusion

Treatment: Drugs: Topotecan
Topotecan for injection

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS) - OS will be derived as: (date of death - date of randomization) + 1. Subjects who are alive or permanently lost to follow-up at the cut-off date for the analysis will be censored at the last date the subject was known to be alive.
Timepoint [1] 0 0
Up to approximately 2.5 years
Secondary outcome [1] 0 0
Progression-free survival (PFS) - PFS will be defined as the time from the date of randomization to the date of first documentation of tumor progression or death from any cause, whichever occurs first.
Timepoint [1] 0 0
Up to approximately 2.5 years
Secondary outcome [2] 0 0
Objective response rate (ORR) - The ORR is the percentage of subjects with best overall response of either complete response (CR) or partial response (PR).
Timepoint [2] 0 0
Up to approximately 2.5 years
Secondary outcome [3] 0 0
Clinical benefit rate (CBR) - The CBR is defined as the proportion of subjects with either a CR, PR, or stable disease (SD), relative to the number of subjects in the treatment group.
Timepoint [3] 0 0
Up to approximately 2.5 years
Secondary outcome [4] 0 0
Area under the concentration versus time curve (AUC) of dinutuximab - The area under the plot of plasma concentration of dinutuximab against time after administration
Timepoint [4] 0 0
Approximately 4 months
Secondary outcome [5] 0 0
Maximum concentration (Cmax) of dinutuximab - Cmax is a measure of the highest concentration of dinutuximab in the blood that is measured after a dose.
Timepoint [5] 0 0
Approximately 4 months
Secondary outcome [6] 0 0
Halt-life (t1/2) of dinutuximab - The half-life represents the time it takes for the dinutuximab concentration in the body to be reduced by 50%.
Timepoint [6] 0 0
Approximately 4 months
Secondary outcome [7] 0 0
Clearance (CL) of dinutuximab - Clearance is a measure of the body's efficiency in eliminating dinutuximab.
Timepoint [7] 0 0
Approximately 4 months
Secondary outcome [8] 0 0
Incidence of adverse events - The incidence of adverse events among subjects throughout the study will be measured by the number of subjects analyzed and the percentage of subjects who experienced an adverse event.
Timepoint [8] 0 0
Up to approximately 2.5 years
Secondary outcome [9] 0 0
Incidence of toxicities - The incidence of toxicities will be determined by the percentage of subjects who experienced a laboratory abnormality, among all subjects exposed to each treatment.
Timepoint [9] 0 0
Up to approximately 2.5 years

Eligibility
Key inclusion criteria
1. Have histologically or cytologically confirmed SCLC (undifferentiated small-cell
carcinoma arising in or consistent with lung cancer origin).

2. Documented relapse or disease progression during or after first-line platinum-based
therapy (subjects refractory to initial platinum-based therapy are eligible).

3. Have no curative therapy available.

4. Have a life expectancy of at least 12 weeks.

5. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Have adequate bone marrow and hepatic function.

7. Have calculated creatinine clearance (CrCL) =30 mL/minute or serum creatinine =1.5
times below the upper limit of normal.

8. Women of reproductive potential must not be pregnant or breastfeeding and have a
negative urine or serum pregnancy test obtained within 7 days prior to the first dose
of study treatment.

9. Subjects must agree to consistently use 2 forms of highly effective
contraception/birth control between signing of the informed consent and 60 days after
the last study drug administration.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Candidate for re-treatment with original platinum-based regimen as second-line
therapy.

2. Prior treatment with irinotecan, topotecan, or dinutuximab.

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.

4. Have mixed small cell and non-small cell histologic features.

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.

6. Have a history or current evidence of uncontrolled cardiovascular disease.

7. Have not recovered from prior surgery, significant trauma, systemic anticancer
therapy, radiation therapy or investigational therapy to Grade 1 or better toxicity
prior to enrollment (Part 1) or randomization (Part 2).

8. Have had organ allograft or hematopoietic transplantation.

9. Known to be human immunodeficiency virus (HIV) positive.

10. Have an active infection requiring treatment or one that is clinically serious in the
Investigator's opinion.

11. Have received a live vaccine within 6 months of enrollment (Part 1) or randomization
(Part 2).

12. Exposure to strong CYP3A4 and/or UGT1A1 inhibitors and strong CYP3A4 inducers within
14 days of enrollment (Part 1) or randomization (Part 2).

13. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Mid North Coast Cancer Institute Coff Habour Health Campus - Coffs Harbour
Recruitment hospital [2] 0 0
Mater Misericordiae Limited and Mater Medical Research Institute Limited - South Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Ballarat Health Services - Ballarat
Recruitment postcode(s) [1] 0 0
NSW 2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
QLD 4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3350 - Ballarat
Recruitment outside Australia
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Alaska
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Bangkok
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Kiev
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Odessa
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Vinnitsya
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
United Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a 2-part, multicenter, open-label, randomized study of dinutuximab and irinotecan
versus irinotecan alone in subjects with relapsed or refractory small cell lung cancer
(SCLC). Part 1 of the study involves intrasubject dose escalation to evaluate the safety and
tolerability of dinutuximab in combination with irinotecan. Part 2 of the study is designed
to determine whether dinutuximab plus irinotecan prolongs overall survival (OS) compared with
irinotecan alone. Subjects in Part 2 will be randomized in a 2:2:1 fashion to 1 of 3
treatment groups: (A) irinotecan; (B) dinutuximab plus irinotecan; or (C) topotecan.
Randomization will be stratified by duration of response to prior platinum therapy
(relapse-free period <3 months or =3 months).
Trial website
https://clinicaltrials.gov/show/NCT03098030
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications