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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 information initially 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
Hospital Avenue
Nedlands
Western Australia 6009
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
This is a study to determine the maximum dose of CP-870,893 that can be safely administered in combination with standard chemotherapy (cisplatin and pemetrexed) as the treatment of patients with malignant pleural mesothelioma that can't be removed surgically.

Who is it for?
You can join this study if you have malignant pleural mesothelioma that cannot be removed surgically and are planned to receive treatment with standard chemotherapy (cisplatin and pemetrexed) .

Trial details:
Participants will receive standard treatment with cisplatin and pemetrexed chemotherapy which is given intravenously every 3 weeks, with the addition of CP-870,893 (CD40 activating antibody) on day 8 of each cycle. CP-870,893 activates the immune system which might help treat the cancer. Assessment for side effects by patient questionnaires and assessment by health professional, and collection of blood tests will occur weekly whilst on treatment and at 90-day follow-up visit. Tumour response will be measured with scans after the first cycle of treatment (PET scan), and after every 2 cycles of treatment (CT scan). The study aims to determine the maximum dose, side effects and effectiveness of CP-870,893 that can be safely administered in combination with standard chemotherapy as the first line treatment for malignant mesothelioma. It will also help to characterise the body's immune response to the treatment.
After the maximum dose of CP-870,893 has been determined, 6 patients receiving the treatment at the maximum dose will have biopsies taken of the cancer before treatment starts and at the completion of treatment.
Trial website
Trial related presentations / publications
Nowak AK, Cook AM, McDonnell AM et al. A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma. Annals of Oncology (2015) 26: 2483–2490. doi:10.1093/annonc/mdv387

McDonnell AM, Cook A, Robinson BWS, Lake RA and Nowak AK. Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals
consistent and cyclical modulation of T cell and dendritic cell parameters. BMC Cancer (2017) 17:417. DOI 10.1186/s12885-017-3403-5
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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Nowak AK, Cook AM, McDonnell AM et al. A phase 1b ... [More Details]
Study results articleYes McDonnell et al. BMC Cancer (2017) 17:417 DOI 10.... [More Details]

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.