The primary objective is to determine the effect on progression-free survival (PFS) of adding MORAb-009 to the combination of pemetrexed and cisplatin in the treatment of subjects with unresectable malignant pleural mesothelioma (MPM). (Protocol ch…
ID
Source
Brief title
Condition
- Mesotheliomas
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is PFS at 6 months. PFS is defined as time from
the date of first dose of MORAb-009 to the date of disease progression or death
due to any cause. A *response*, in terms of PFS, is defined to be at least a 6
month stabilization of disease.
Safety endpoints (protocol 9.6, page 66) include
- assessment of incidence and severity of AEs, including clinical laboratory
parameters, physical examination, ECG, pulmonary function testing and HACA
development.
- Tolerability of treatment: The number of subjects discontinuing treatment due
to toxicity and the number of subjects who delay treatment or skip all or part
of cycles of treatment due to toxicity and the extent of delays.
Secondary outcome
Secundary efficacy endpoints are (protocol 9.5, page 66):
- ORR (defined as the proportion of subjects with a partial response (PR) or
complete response (CR))
- duration of this response (defined as as the time from first documentation of
objective tumor response to the first documentation of objective tumor
progression or to death due to any cause)
- overall survival (defined as the time from the date of the first dose of
MORAb-009 to the date of death)
- overall median progression free survival
- To determine the safety and tolerability of MORAb-009 when administered with
pemetrexed and cisplatin.
Exploratory endpoints:
- Change in CA-125 Levels
- Change in Karnofsky Performance Status
- Analysis of survival by HLA subtype (if sufficient data on HLA subtype are
available)
- Molecular marker analysis
Background summary
Mesothelioma is an aggressive malignancy that is almost uniformly fatal, with a
median survival of approximately 9-12 months. The regimen of pemetrexed plus
cisplatin is now the standard of care for newly diagnosed subjects with
mesothelioma. Although this regimen represents a significant advance in the
treatment of mesothelioma, the median survival of subjects is only 12.1 months
and there is clearly a need to develop better therapeutic regimens to improve
the outcome of these subjects. Given the fact that MORAb-009 was generally
well-tolerated in the Phase 1 study and the possibility of clinical benefit in
mesothelin-positive tumors, this Phase 2 study of the efficacy of MORAb-009 in
combination with conventional chemotherapeutic agents in unresectable MPM is
being undertaken. (Protocol 3.2, page 24.)
Study objective
The primary objective is to determine the effect on progression-free survival
(PFS) of adding MORAb-009 to the combination of pemetrexed and cisplatin in the
treatment of subjects with unresectable malignant pleural mesothelioma (MPM).
(Protocol ch 2, page 22.)
Study design
See figure 1, page 25 of the protocol for the protocol schema. If a patient
will be eligible for the study, a maximum of 6 21-day cycles of the combination
treatment MORAb-009, CIsplatin and Pemetrexed will be administered. MORAb-009
will be administered on day 1 and 8 of every cycle, Pemetrexed and Cisplatin on
day 1 of every cycle.
After the combination treatment, patients can continue MORAb-009 monotherapy
until disease progression. Hereafter, only an 'End of Treatment' visit will be
scheduled. Subjects will be contacted monthly for the first 9 months and every
other month thereafter for survival status and any new anti-cancer therapies
until death or the end of the trial.
Intervention
All patients will receive intravenous MORAb-009 in a dose of 5.0 mg/kg on day 1
and 8 of every cycle. Pemetrexed will be intravenously administered at a dose
of 500 mg/m2 in approximately 10 minutes. The protocol describes how the
chemotherapy should be administered, but the centres are allowed to use their
local standard practice for this. Approximately 30 minutes thereafter the
intravenous Cisplatin infusion will commence at a dose of 75 mg/m2. This
infusion will take ppproximately 2 hours.
Study burden and risks
Refer to the flow chart page 56 for an overview of all study procedures. Refer
to section E of the ABR form for an overview of the burden and risks associated
with participation.
210 Welsh Pool Road
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210 Welsh Pool Road
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Listed location countries
Age
Inclusion criteria
- >= 18 years of age
- Life expectancy of at least 3 months
- Confirmed diagnosis of MPM with the following characteristics: unresectable disease (or otherwise not a candidate for curative surgery); or epithelial type or biphasic (mixed) type with low sarcomatous content).
- Measurable disease at Screening
- Karnofsky performance status of >= 70% at Screening
- Other significant medical conditions must be well-controlled and stable
- Laboratory results must be within a certain range (see page 26)
- serum creatinine clearance >= 60 mL/min
- Subjects must be sterile or using adequate contraception during the study and for at least 8 weeks after the last dose of MORAb-009
- willing and able to sign informed consent
Exclusion criteria
- Sarcomatous type of mesothelioma
- Prior systemic therapy or radiotherapy
- central nervous system (CNS) tumor involvement
- other active malignancy requiring treatment
- clinically significant heart disease or arrhythmias
- hepatitis or HIV infection
- active serious systemic disease
- Treatment within 3 months of the start of the trial with other immunomodulatory therapy
- hypersensitivity to one of the medications which will be administered
- breast-feeding, pregnant, or likely to become pregnant
- not willing or unable to sign informed consent
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-005448-18-NL |
| ClinicalTrials.gov | NCT00738582 |
| CCMO | NL26231.078.09 |