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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03317496




Registration number
NCT03317496
Ethics application status
Date submitted
29/09/2017
Date registered
23/10/2017

Titles & IDs
Public title
Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies
Scientific title
A MULTICENTER, OPEN-LABEL, PHASE 1B/2 STUDY TO EVALUATE SAFETY AND EFFICACY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH CHEMOTHERAPY WITH OR WITHOUT OTHER ANTI-CANCER IMMUNOTHERAPIES AS FIRST-LINE TREATMENT IN PATIENTS WITH ADVANCED MALIGNANCIES
Secondary ID [1] 0 0
B9991023
Secondary ID [2] 0 0
B9991023
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab 800 mg in combination with pemetrexed / carboplatin
Treatment: Drugs - Avelumab 800 mg in combination with gemcitabine / cisplatin.
Treatment: Drugs - Avelumab 1200 mg in combination with pemetrexed/carboplatin
Treatment: Drugs - Avelumab 1200 mg in combination with gemcitabine/cisplatin

Experimental: Group A Cohort A1 - Non-squamous non-small cell lung cancer (NSCLC) patients treated with 800 mg avelumab plus pemetrexed/carboplatin

Experimental: Group A Cohort A2 - Cisplatin-eligible urothelial cancer (UC)patients treated with 800 mg avelumab plus gemcitabine/cisplatin

Experimental: Group A Cohort A3 - Non-squamous non-small cell lung cancer (NSCLC) patients treated with 1200 mg avelumab plus pemetrexed/carboplatin

Experimental: Group A Cohort A4 - Cisplatin-eligible urothelial cancer (UC) patients treated with 1200 mg avelumab plus gemcitabine/cisplatin


Treatment: Drugs: Avelumab 800 mg in combination with pemetrexed / carboplatin
Avelumab Pemetrexed Carboplatin

Treatment: Drugs: Avelumab 800 mg in combination with gemcitabine / cisplatin.
Avelumab Gemcitabine Cisplatin

Treatment: Drugs: Avelumab 1200 mg in combination with pemetrexed/carboplatin
Avelumab Pemetrexed Carboplatin

Treatment: Drugs: Avelumab 1200 mg in combination with gemcitabine/cisplatin
Avelumab Gemcitabine Cisplatin
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT)
Timepoint [1] 0 0
Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)
Primary outcome [2] 0 0
Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
Timepoint [2] 0 0
From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)
Secondary outcome [1] 0 0
Serum Concentration of Avelumab
Timepoint [1] 0 0
Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days)
Secondary outcome [2] 0 0
Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue
Timepoint [2] 0 0
Pre-dose on Day 1 of Cycle 1
Secondary outcome [3] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [3] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)
Secondary outcome [4] 0 0
Number of Participants With Treatment Related TEAEs
Timepoint [4] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)
Secondary outcome [5] 0 0
Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03
Timepoint [5] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)
Secondary outcome [6] 0 0
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade
Timepoint [6] 0 0
From screening up to 90 days after last dose of study drug (maximum up to 5 years approximately)
Secondary outcome [7] 0 0
Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies for Avelumab
Timepoint [7] 0 0
From first dose of study drug up to last dose of study drug (maximum up to 5 years approximately)
Secondary outcome [8] 0 0
Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment
Timepoint [8] 0 0
From start of treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5 years approximately)
Secondary outcome [9] 0 0
Overall Survival (OS)
Timepoint [9] 0 0
From first dose of study treatment until death due to any cause (maximum up to 5 years approximately)
Secondary outcome [10] 0 0
Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment
Timepoint [10] 0 0
From date of first documented response to date of first documented PD or death due to any cause, whichever occurred first (maximum up to 5 years approximately)
Secondary outcome [11] 0 0
Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment
Timepoint [11] 0 0
From first dose of study treatment until first documentation of CR or PR (maximum up to 5 years approximately)
Secondary outcome [12] 0 0
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression
Timepoint [12] 0 0
Baseline and Cycle 2 Day 8 (each cycle of 21 days)

Eligibility
Key inclusion criteria
1. Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumor that is not amenable for treatment with curative intent as follows:

* For all groups:
* Measurable disease by RECIST v1.1 with at least 1 measurable lesion, and availability of tumor specimen 18 months or less old.
* No prior systemic treatment for unresectable locally advanced or metastatic disease for the tumor type under study. If prior systemic chemotherapy treatment was given in the adjuvant or neo-adjuvant setting or as part of radiotherapy chemotherapy treatment, disease-free interval after stop of systemic treatment must be more than 6 months for non-squamous NSCLC and more than 12 months for UC;
* Cohort A1 and Cohort A3: Non-squamous NSCLC, with no activating EGFR mutations, ALK or ROS1 translocations/rearrangements. If monotherapy pembrolizumab is available as a standard of care treatment option, patients must have a tumor proportion score (TPS) <50% for PD L1 (via the 22C3 pharmDx or the Ventana (SP263) PD L1 IHC assay).
* Cohort A2 and Cohort A4: Transitional cell carcinoma of the urothelium including the bladder, urethra, renal pelvis, and ureter.
2. ECOG performance status 0 or 1
3. Estimated life expectancy of at least 90 days
4. Adequate bone marrow, renal, and liver function
5. Negative serum pregnancy test at screening
6. Signed and dated informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior immunotherapy with any antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
2. Patients with known symptomatic central nervous system metastases requiring steroids.
3. Diagnosis of other malignancy within 2 years prior to enrollment except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the bladder, breast, or cervix, or low grade (Gleason =6) prostate cancer
4. Use of immunosuppressive medication at the time of enrollment
5. Active or prior autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
6. Prior organ transplantation including allogenic stem cell transplantation
7. Active infection requiring systemic therapy
8. Known history of HIV or AIDS
9. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
10. Administration of live vaccine within 4 weeks prior to study entry
11. Known prior severe hypersensitivity to the investigational products or any component in their formulations,
12. Known prior severe hypersensitivity to platinum-related compounds for all cohorts, to pemetrexed for patients enrolled in Cohort A1 and Cohort A3, and to gemcitabine for patients enrolled in Cohort A2 and Cohort A4
13. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade > 1)
14. Known history of colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
15. Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade 2 or prolongation of the QTcF interval to >480 msec.
16. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
17. Major surgery =28 days or major radiation therapy =14 days prior to enrollment.
18. Participation in other studies involving investigational drug(s) within 28 days prior to study entry.
19. Concurrent treatment with a prohibited medication.
20. Other acute or chronic medical or psychiatric condition
21. Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilling or unable to use at least 1 highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of chemotherapy (for male and female patients) or at least 30 days after the last dose of avelumab (for female patients), whichever is longer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/12/2022
Sample size
Target
Accrual to date
Final
67
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
St Vincent's Public Hospital Sydney - Darlinghurst
Recruitment hospital [4] 0 0
Western Health, Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Czechia
State/province [5] 0 0
Olomouc
Country [6] 0 0
Czechia
State/province [6] 0 0
Prague
Country [7] 0 0
Czechia
State/province [7] 0 0
Praha 2
Country [8] 0 0
Hungary
State/province [8] 0 0
Budapest
Country [9] 0 0
Italy
State/province [9] 0 0
AN
Country [10] 0 0
Italy
State/province [10] 0 0
FC
Country [11] 0 0
Italy
State/province [11] 0 0
MB
Country [12] 0 0
Italy
State/province [12] 0 0
MI
Country [13] 0 0
Italy
State/province [13] 0 0
Napoli
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Valencia
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Cornwall
Country [18] 0 0
United Kingdom
State/province [18] 0 0
England
Country [19] 0 0
United Kingdom
State/province [19] 0 0
South Yorkshire
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03317496