Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03098030
Ethics application status
Date submitted
22/03/2017
Date registered
31/03/2017
Date last updated
9/12/2020

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
Treatment: Other - 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 (16 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.


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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 2.5 years
Secondary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 2.5 years
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
Up to approximately 2.5 years
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR)
Timepoint [3] 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
Sex
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
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
1/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/03/2020
Sample size
Target
Accrual to date
Final
483
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Montana
Country [13] 0 0
United States of America
State/province [13] 0 0
New Mexico
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
South Dakota
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
United States of America
State/province [23] 0 0
West Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Blagoevgrad
Country [26] 0 0
Bulgaria
State/province [26] 0 0
Burgas
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Dobrich
Country [28] 0 0
Bulgaria
State/province [28] 0 0
Gabrovo
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Panagyurishte
Country [30] 0 0
Bulgaria
State/province [30] 0 0
Pleven
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Plovdiv
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Sofia
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Varna
Country [34] 0 0
Canada
State/province [34] 0 0
Alberta
Country [35] 0 0
Canada
State/province [35] 0 0
New Brunswick
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
France
State/province [38] 0 0
Alpes-Côte d'Azur
Country [39] 0 0
France
State/province [39] 0 0
Occitanie
Country [40] 0 0
France
State/province [40] 0 0
Pays De La Loire
Country [41] 0 0
France
State/province [41] 0 0
Rhône-Alpes
Country [42] 0 0
France
State/province [42] 0 0
Brest
Country [43] 0 0
France
State/province [43] 0 0
Caen
Country [44] 0 0
France
State/province [44] 0 0
Créteil
Country [45] 0 0
France
State/province [45] 0 0
Marseille
Country [46] 0 0
France
State/province [46] 0 0
Saint-Herblain
Country [47] 0 0
France
State/province [47] 0 0
Strasbourg
Country [48] 0 0
Georgia
State/province [48] 0 0
Batumi
Country [49] 0 0
Georgia
State/province [49] 0 0
Tbilisi
Country [50] 0 0
Hong Kong
State/province [50] 0 0
Kowloon
Country [51] 0 0
Hong Kong
State/province [51] 0 0
Pokfulam
Country [52] 0 0
Hungary
State/province [52] 0 0
Jasz-Nagykun-Szolnok
Country [53] 0 0
Hungary
State/province [53] 0 0
Budapest
Country [54] 0 0
Hungary
State/province [54] 0 0
Farkasgyepu
Country [55] 0 0
Hungary
State/province [55] 0 0
Matrahaza
Country [56] 0 0
Hungary
State/province [56] 0 0
Miskolc
Country [57] 0 0
Hungary
State/province [57] 0 0
Tatabanya
Country [58] 0 0
Hungary
State/province [58] 0 0
Torokbalint
Country [59] 0 0
Hungary
State/province [59] 0 0
Zalaegerszeg
Country [60] 0 0
India
State/province [60] 0 0
Karnataka
Country [61] 0 0
India
State/province [61] 0 0
Maharashtra
Country [62] 0 0
India
State/province [62] 0 0
Rajasthan
Country [63] 0 0
India
State/province [63] 0 0
Bangalore
Country [64] 0 0
India
State/province [64] 0 0
Jaipur
Country [65] 0 0
Italy
State/province [65] 0 0
Catania
Country [66] 0 0
Italy
State/province [66] 0 0
Milan
Country [67] 0 0
Italy
State/province [67] 0 0
Perugia
Country [68] 0 0
Italy
State/province [68] 0 0
Rome
Country [69] 0 0
Italy
State/province [69] 0 0
Siena
Country [70] 0 0
Italy
State/province [70] 0 0
Torino
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Busan
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Chungcheongbuk-do
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Daegu
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Daejeon
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Gyeonggi-do
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Gyeongsangnam-do
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Incheon
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Jeonnam
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Namdong
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Seoul
Country [81] 0 0
Korea, Republic of
State/province [81] 0 0
Ulsan
Country [82] 0 0
Korea, Republic of
State/province [82] 0 0
Wonju-Si, Gangwon-do
Country [83] 0 0
Lithuania
State/province [83] 0 0
Kaunas
Country [84] 0 0
Lithuania
State/province [84] 0 0
Vilnius
Country [85] 0 0
Malaysia
State/province [85] 0 0
Kuala Lumpur
Country [86] 0 0
Malaysia
State/province [86] 0 0
Kuching
Country [87] 0 0
Malaysia
State/province [87] 0 0
Putrajaya
Country [88] 0 0
Philippines
State/province [88] 0 0
Cebu City
Country [89] 0 0
Philippines
State/province [89] 0 0
Davao City
Country [90] 0 0
Philippines
State/province [90] 0 0
Manila
Country [91] 0 0
Philippines
State/province [91] 0 0
Quezon City
Country [92] 0 0
Poland
State/province [92] 0 0
Pomeranian Voivodeship
Country [93] 0 0
Poland
State/province [93] 0 0
Warminsko-Mazurskie
Country [94] 0 0
Poland
State/province [94] 0 0
Mrozy
Country [95] 0 0
Poland
State/province [95] 0 0
Otwock
Country [96] 0 0
Poland
State/province [96] 0 0
Pilchowice
Country [97] 0 0
Poland
State/province [97] 0 0
Poznan
Country [98] 0 0
Poland
State/province [98] 0 0
Warszawa
Country [99] 0 0
Poland
State/province [99] 0 0
Lódz Voivodeship
Country [100] 0 0
Romania
State/province [100] 0 0
Baia-Mare
Country [101] 0 0
Romania
State/province [101] 0 0
Cluj-Napoca
Country [102] 0 0
Romania
State/province [102] 0 0
Craiova
Country [103] 0 0
Romania
State/province [103] 0 0
Satu-Mare
Country [104] 0 0
Romania
State/province [104] 0 0
Suceava
Country [105] 0 0
Romania
State/province [105] 0 0
Timisoara
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Arkhangelsk
Country [107] 0 0
Russian Federation
State/province [107] 0 0
Ekaterinburg
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Kursk
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Moscow
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Novosibirsk
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Omsk
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Orenburg
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Saint Petersburg
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Saint-Petersburg
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Samara
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Yaroslavl
Country [117] 0 0
Slovakia
State/province [117] 0 0
Bardejov
Country [118] 0 0
Slovakia
State/province [118] 0 0
Žilina
Country [119] 0 0
Spain
State/province [119] 0 0
Alicante
Country [120] 0 0
Spain
State/province [120] 0 0
Cantabria
Country [121] 0 0
Spain
State/province [121] 0 0
Galicia
Country [122] 0 0
Spain
State/province [122] 0 0
Madrid
Country [123] 0 0
Spain
State/province [123] 0 0
Navarra
Country [124] 0 0
Spain
State/province [124] 0 0
Barcelona
Country [125] 0 0
Spain
State/province [125] 0 0
Córdoba
Country [126] 0 0
Spain
State/province [126] 0 0
Girona
Country [127] 0 0
Spain
State/province [127] 0 0
Lugo
Country [128] 0 0
Spain
State/province [128] 0 0
Málaga
Country [129] 0 0
Spain
State/province [129] 0 0
Ourense
Country [130] 0 0
Spain
State/province [130] 0 0
Planta
Country [131] 0 0
Spain
State/province [131] 0 0
Sabadell
Country [132] 0 0
Spain
State/province [132] 0 0
Sevilla
Country [133] 0 0
Spain
State/province [133] 0 0
Valencia
Country [134] 0 0
Spain
State/province [134] 0 0
Vigo
Country [135] 0 0
Spain
State/province [135] 0 0
Zaragoza
Country [136] 0 0
Taiwan
State/province [136] 0 0
Kaohsiung City
Country [137] 0 0
Taiwan
State/province [137] 0 0
Taichung City
Country [138] 0 0
Taiwan
State/province [138] 0 0
Tainan City
Country [139] 0 0
Taiwan
State/province [139] 0 0
Taoyuan City
Country [140] 0 0
Thailand
State/province [140] 0 0
Bangkok
Country [141] 0 0
Thailand
State/province [141] 0 0
Chiang Mai
Country [142] 0 0
Thailand
State/province [142] 0 0
Khon Kaen
Country [143] 0 0
Thailand
State/province [143] 0 0
Phitsanulok
Country [144] 0 0
Thailand
State/province [144] 0 0
Songkhla
Country [145] 0 0
Ukraine
State/province [145] 0 0
Dnipropetrovsk
Country [146] 0 0
Ukraine
State/province [146] 0 0
Zakarpattia
Country [147] 0 0
Ukraine
State/province [147] 0 0
Chernivtsi
Country [148] 0 0
Ukraine
State/province [148] 0 0
Kiev
Country [149] 0 0
Ukraine
State/province [149] 0 0
Odessa
Country [150] 0 0
Ukraine
State/province [150] 0 0
Vinnitsya
Country [151] 0 0
United Kingdom
State/province [151] 0 0
Essex
Country [152] 0 0
United Kingdom
State/province [152] 0 0
London
Country [153] 0 0
United Kingdom
State/province [153] 0 0
Leeds
Country [154] 0 0
United Kingdom
State/province [154] 0 0
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/study/NCT03098030
Trial related presentations / publications
Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernandez Nunez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. doi: 10.1016/j.lungcan.2022.03.003. Epub 2022 Mar 4.
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
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03098030