Study MX39795 will compare the efficacy and safety of molecularly-guided therapy versusstandard platinum-containing chemotherapy in patients with poor prognosis cancer of unknown primary site(CUP; non-specific subset) who have achieved disease…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the efficacy of molecularlyguided therapy versus platinum
chemotherapy in term of Progressionfree survival in patients with CUP
whose best response to 3 cycles of platinum induction chemotherapy was assessed
CR, PR or SD
Secondary outcome
To evaluate the efficacy of molecularly guided therapy versus platinum
chemotherapy in terms of overall survival, objective response rate, duration of
response and disease control rate.
For further objectives and details see: Synopsis Table 1
Background summary
Cancer of unknown primary site (CUP) is defined as a histologically-confirmed
metastatic cancer for which a standardized diagnostic work-up fails to identify
the site of origin at the time of diagnosis.
A standardized diagnostic work-up in this context includes mainly:
•*A histopathological review of biopsy material using immunohistochemistry (IHC)
•*A detailed medical history of the patient
•*A complete physical examination (including pelvic and rectal examination)
•*A full blood count and biochemistry analysis
•*Urinalysis and stool occult blood tests
•*A computed tomography (CT) scan of the thorax, abdomen and pelvis
•*A mammography scan and breast MRI (in certain cases)
CUP accounts for 3% to 5% of all malignancies. The disease has a median age of
occurrence of approximately 60 years, is rare in children, and is marginally
more frequentin males. Survival of patients with CUP is poor, with a median
overall survival (OS) of 8-11 months and a one-year survival rate of 25%.
For more information about the background see section 1 of the protocol
Study objective
Study MX39795 will compare the efficacy and safety of molecularly-guided
therapy versus
standard platinum-containing chemotherapy in patients with poor prognosis
cancer of unknown primary site
(CUP; non-specific subset) who have achieved disease control (CR, PR or SD)
after 3 cycles of first-line platinum based induction chemotherapy.
Molecularly-guided therapies will include 8 targeted cancer therapy regimens
and 2 cancer immunotherapy regimens, and will be chosen based on each patient*s
comprehensive genomic profile (see below for further details).
For specific information about the objectives zie table 4 of the protocol
Study design
Study MX39795 is a phase II, randomized, open-label, active-controlled,
multi-center trial. The study will consist of a Screening Period, an Induction
Period including an End of Induction Workup, a Pre-Treatment Work-up, a
Treatment Period, an End of Treatment Visit occurring 30 (± 7) days from last
treatment or at initiation of other anti-cancer therapy (whichever occurs
first), and a Follow-Up Period. The first day of treatment during the Induction
Period will be Day 1 (baseline) of the study.
For a schematic overview of the study design see figure 2 of the protocol
Intervention
Patients will be treated with 3 cycles of chemotherapy in the induction phase
of the study. In the treatment phase subjects will be treated with either
chemotherapy or one of the targeted therapies. Depending on results from the
induction phase, randomization and genomic profiling.
Study burden and risks
The general burden for the patiënt consists, a.o., of bloodsamples (every
cycle), possible collection of a tumorsample, and the administration of
chemotherapy and specific investigational products (every cycle, depending on
the phase of the study the patient is in) that may lead to various adverse
events.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
• Age >=18 years
• Histologically-confirmed unresectable CUP
• At least one lesion that is measurable according to Response Evaluation
Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Availability of a tumor Formalin-fixed paraffin-embedded(FFPE) block <=4
months old at Screening that is expected to be sufficient and suitable (in
quantity and quality) for generation of a Foundation medicine tissue biopsy
assay comprehensive genomic profile at a central reference pathology laboratory
• Availability of test reports confirming local CUP diagnosis If test reports
confirming local CUP diagnosis are not available, an FFPE block must be
submitted that is sufficient to allow for central confirmation of CUP
diagnosis
• No prior systemic therapy for the treatment of CUP
• Prior local intratumoral therapy may be accepted. If prior local intratumoral
therapy, at least one of the measurable lesion(s) must have not benefited from
local intratumoral therapy
• ECOG performance status of 0 or 1
• Life expectancy >=12 weeks
• Eligible for platinum-based chemotherapy
• Adequate hematologic and end-organ function
• Use of appropriate contraceptive methods
Exclusion criteria
- Squamous cell CUP
- Patients with histology and immunohistology profiles (per 2015 ESMO
guidelines) that are not adenocarcinoma or poorly differentiated carcinoma /
adenocarcinoma)
- Patient with an immunohistochemistry profile that provides a definitive
clinical indication of a primary cancer with a specific treatment
-Patients who can be assigned to a specific subset of CUP for which a specific
treatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP
or with a clinical and IHC profile indicative of a specific primary tumor are
also excluded. These are:
- Poorly differentiated carcinoma with midline distribution
- Women with papillary adenocarcinoma of the peritoneal cavity
- Women with adenocarcinoma involving only the axillary lymph nodes
- Squamous cell carcinoma of the cervical lymph nodes
- Poorly differentiated neuroendocrine tumors
- Men with blastic bone metastases and elevated PSA
- Patients with a single, small, potentially resectable tumor
- Colon cancer-type CUP
- CK7 positive, CK20 negative and TTF-1 positive tumors in a context suggestive
of lung adenocarcinoma or thyroid cancer, IHC profile definitely indicative of
breast cancer OR an IHC profile indicative of breast cancer and either a
history of breast cancer or lymph nodes in the drainage areas of the breast,
high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a
mass in the gynecological tract or any tumor mass or lymph node in the
abdominal cavity, IHC profile suggestive of renal cell carcinoma and renal
lesions, with a Bosniak classification higher than IIF, IHC profile compatible
with cholangiocarcinoma or pancreatobiliary and 1 or 2 liver lesions without
extrahepatic disease or with only pulmonary metastases and/or lymph nodes in
the drainage areas of the liver
-Known presence of brain or spinal cord metastasis (including metastases that
have been
irradiated only), as determined by CT or magnetic resonance imaging (MRI)
evaluation during screening
-History or known presence of leptomeningeal disease
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 | EUCTR 2017-003040-2-NL |
| ClinicalTrials.gov | NCT03498521 |
| CCMO | NL69436.056.19 |