A phase III, open-label, multiarm study to assess the efficacy of immunotherapy together with standard of care in patients diagnosed with extensive stage Small-Cell Lung Cancer

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2016-001203-23-ES
• Date of registration: 07/02/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A phase III, open-label, multiarm study to assess the efficacy of immunotherapy together with standard of care in patients diagnosed with extensive stage Small-Cell Lung Cancer
• Scientific title: A Phase III, Randomized, Multicenter, Open-Label, Comparative Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for the First-Line Treatment in Patients with Extensive Disease (Stage IV) Small-Cell Lung Cancer (SCLC) - A Phase III Randomised Study of Durva+/- Treme combined with SoC as 1st line treatment in ED-SCLC Pt
• Date of first enrolment: 16/03/2017
• Target sample size: 795
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001203-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, China, Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Slovakia, Spain, Taiwan, Turkey, Ukraine, United States

Contacts

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage IV SCLC [T any, N any, M1 a/b]), including patients with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment.
2. Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.
3. Life expectancy =12 weeks at Day 1.
4. ECOG 0 or 1 at enrolment.
5. No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines.
6 .Body weight >30 kg.
7. Adequate organ and marrow function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 477
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 318

Exclusion criteria:
1. Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest).
2. Any other concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
3. History of allogenic organ transplantation.
4. Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS
5. Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
6. History of another primary malignancy
7. Active infection including tuberculosis, HIV, hepatitis B anc C
8. Current or prior use of immunosuppressive medication within 14 days before the first IP dose
9. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control..
10. Past medical history of interstitial lung disease, drug-induced pneumonitis, or any evidence of clinically active interstitial lung disease.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

First-line patients with extensive disease (Stage IV) small-cell lung cancer (SCLC)
MedDRA version: 19.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: tremelimumab
Product Code: MEDI1123
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tremelimumab
CAS Number: 745013-19-6
Current Sponsor code: MEDI1123
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Carboplatin
Product Name: Carboplatin
Product Code: 61703-339-56
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: carboplatin
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Cisplatin
Product Name: Cisplatin
Product Code: 63323-103
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: cisplatin
CAS Number: 15663-27-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: etoposide
Product Name: Etoposide
Product Code: 63323-104
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: etoposide
CAS Number: 33419-42-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): 1.Overall survival (OS)- the time from the date of randomization until death due to any cause.
2.Progression free survival (PFS)- the time from the date of randomization until the date of objective disease progression or death.

Secondary Objective: 1.To further assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP in terms of ORR, APF6, APF12 and OS 18.
2.To assess the efficacy of durvalumab + EP compared with EP in terms of ORR, PFS, OS, APF6, APF12, and OS18.
3.To assess the efficacy of durvalumab + tremelimumab + EP treatment compared with durvalumab + EP in terms of PFS and OS.
4.To assess the PK of both durvalumab and durvalumab + tremelimumab.
5.To investigate the immunogenicity of durvalumab and durvalumab + tremelimumab.
6.To assess the effect of the treatment on changes in symptoms and health-related QoL using EORTC QLQ-C30 v3 and QLQ-LC13.
7.Safety objective: To assess the safety and tolerability profile of durvalumab and durvalumab + tremelimumab in combination with EP treatment compared with EP.

Main Objective: To assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP in terms of overall survival (OS) and progression-free survival ( PFS).

Timepoint(s) of evaluation of this end point: 1. 34 months after the first patient has been randomized
2. 23 months after the first patient has been randomized

Secondary Outcome(s)

Secondary end point(s): 1.Objective Response Rate (ORR) -the number (%) of patients with at least 1 visit response of CR or PR.
2.Proportion of patients alive and progression free at 6 (APF6) and 12 months (APF12).
3. Proportion of patients alive at 18 months (OS18).

Timepoint(s) of evaluation of this end point: 23 months after the first patient has been randomized

Secondary ID(s)

2016-001203-23-HU

D419QC00001

Source(s) of Monetary Support

AstraZeneca AB