Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000294257
Ethics application status
Approved
Date submitted
26/03/2009
Date registered
18/05/2009
Date last updated
22/12/2022
Date data sharing statement initially provided
2/06/2022
Date results provided
22/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
CD-40 activating antibody (CP-870,893) in combination with cisplatin and pemetrexed in unresectable malignant mesothelioma: a phase Ib study
Scientific title
CD-40 activating antibody (CP-870,893) in combination with cisplatin and pemetrexed in unresectable malignant mesothelioma: a phase Ib study to determine the maximum tolerated dose of CP-870,893
Secondary ID [1] 283904 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
unresectable malignant pleural mesothelioma 4530 0
Condition category
Condition code
Cancer 4818 4818 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
addition of CP-870,893 (CD40 activating antibody) to first line treatment with cisplatin (75mg/m2 intravenous injection) and pemetrexed (500mg/m2 intravenous injection) chemotherapy. Chemotherapy to be administered on day 1 of each cycle for a maximum of 6 cycles. CP-870,893 intravenous injection on day 8 of each cycle (starting dose level 0.1mg/kg, dose range for determining tolerability 0.05-2mg/kg) for a maximum of 6 cycles with chemotherapy. Individual participants will receive a specific and fixed dose of CP-870,893. Each cycle is 3 weeks in duration and there will be no planned breaks between cycles. Radiological responders will have the option of continuing treatment with CP-870,893 alone intravenously every 3 weeks for a maximum of a further 6 cycles.
Intervention code [1] 4289 0
Treatment: Drugs
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 5678 0
to determine the maximum tolerated dose of CP-870,893 in combination with up to cisplatin and pemetrexed, as determined by monitoring by health care professionals and patient questionnaires.
Timepoint [1] 5678 0
Toxicity will be monitored weekly through patient questionnaires and by health professionals whilst receiving treatment, and at 90-day follow-up visit.
Secondary outcome [1] 241573 0
toxicity as monitored by patient questionnaires and health professionals.
Timepoint [1] 241573 0
weekly whilst on treatment and at 90-day follow-up visit
Secondary outcome [2] 241574 0
objective tumour response as measured on computerised tomography (CT) scan using modified-Response Evaluation Criteria in Solid Tumour (RECIST) criteria at baseline and every 2 cycles, as well as at 90-day follow-up visit.
Timepoint [2] 241574 0
at baseline, every 2 cycles whilst on treatment, and at 90-day follow-up visit
Secondary outcome [3] 241575 0
tumour response as determined on fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at baseline and after one cycle of treatment (for patients without prior pleurodesis or pleurectomy)
Timepoint [3] 241575 0
at baseline and after one cycle of treatment
Secondary outcome [4] 241576 0
change in laboratory markers of biological response (serum mesothelin, blood analysis for immunology markers)
Timepoint [4] 241576 0
Immunology markers measured at baseline, weekly whilst on treatment, and at 90-day follow-up visit. Serum Mesothelin measured at baseline, every 2 cycles whilst on treatment, and at 90-day follow-up visit.
Secondary outcome [5] 241577 0
change in lymphocyte infiltration and necrosis on tumour biopsy in an expansion cohort of patients at the maximum tolerated dose
Timepoint [5] 241577 0
CT guided biopsy of pleural tumour taken before commencement of treatment (except if previous biopsy sample available) and repeated in third week of cycle 2.

Eligibility
Key inclusion criteria
- histologically or cytologically confirmed malignant pleural mesothelioma
- planned for first-line treatment with cisplatin and pemetrexed
- measurable or evaluable disease on CT (modified RECIST criteria)
- Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0-1
- platelets >100, neutrophils >2
- est. calculated creatinine clearance (CrCl) >/= 60ml/min
- not pregnant or breast feeding
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- unwilling to comply with therapeutic protocol
- bilirubin > upper limit of normal (ULN), alanine transaminase (ALT) or aspartate transaminase (AST) > 2x ULN, alkaline phosphatase (ALP) > 2.5x ULN
- history of severe autoimmune disease
- prior radiotherapy to all areas of measurable disease
- prior history of thromboembolic disorder
- previous or concurrent malignancy (except curatively treated basal cell carcinoma (BCC) of skin, carcinoma-in-situ (CIS) of cervix) unless treated with curative intent >5 years before enrolment
- concomitant requirement for oral corticosteroids for >5 days of each treatment cycle
- symptomatic central nervous system (CNS) involvement

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)
Not applicable; non randomised study.
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2009
Actual
31/03/2010
Date of last participant enrolment
Anticipated
Actual
18/10/2011
Date of last data collection
Anticipated
Actual
10/01/2014
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 4720 0
Commercial sector/Industry
Name [1] 4720 0
Pfizer Australia (research grant-in-aid for investigator initiated study)
Country [1] 4720 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue
Nedlands
Western Australia 6009
Country
Australia
Secondary sponsor category [1] 4265 0
None
Name [1] 4265 0
None
Address [1] 4265 0
None
Country [1] 4265 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6755 0
Sir Charles Gairdner Hospital Human Research Ethics Committee
Ethics committee address [1] 6755 0
Ethics committee country [1] 6755 0
Australia
Date submitted for ethics approval [1] 6755 0
31/03/2009
Approval date [1] 6755 0
26/06/2009
Ethics approval number [1] 6755 0
2008-148

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

Contacts
Principal investigator
Name 29438 0
Prof Anna Nowak
Address 29438 0
Dept of Medical Oncology
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands
WA 6009
Country 29438 0
Australia
Phone 29438 0
+61 8 9346 3333
Fax 29438 0
Email 29438 0
[email protected]
Contact person for public queries
Name 12685 0
Ms Yvonne Demelker
Address 12685 0
University Dept of Medicine and Pharmacology
G block, 4th floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands
Western Australia 6009
Country 12685 0
Australia
Phone 12685 0
+61 8 93463488
Fax 12685 0
+61 8 93462816
Email 12685 0
[email protected]
Contact person for scientific queries
Name 3613 0
Anna Nowak
Address 3613 0
University Dept of Medicine and Pharmacology
G block, 4th floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands
Western Australia 6009
Country 3613 0
Australia
Phone 3613 0
+61 8 93463488
Fax 3613 0
+61 8 93462816
Email 3613 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNovel insights into the pathophysiology and treatment of malignant pleural mesothelioma.2015https://dx.doi.org/10.2217/lmt.15.23
Dimensions AIDexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies2015https://doi.org/10.1080/2162402x.2015.1066062
EmbaseSerial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters.2017https://dx.doi.org/10.1186/s12885-017-3403-5
EmbaseScientific Advances and New Frontiers in Mesothelioma Therapeutics.2018https://dx.doi.org/10.1016/j.jtho.2018.06.011
EmbaseReprogramming Tumor Associated Macrophages toward M1 Phenotypes with Nanomedicine for Anticancer Immunotherapy.2020https://dx.doi.org/10.1002/adtp.201900181
Dimensions AIT-cell agonists in cancer immunotherapy2020https://doi.org/10.1136/jitc-2020-000966
Dimensions AIThe role of macrophage in regulating tumour microenvironment and the strategies for reprogramming tumour-associated macrophages in antitumour therapy2021https://doi.org/10.1016/j.ejcb.2021.151153
N.B. These documents automatically identified may not have been verified by the study sponsor.