None listed
Conditions
Interventions
Induction Period Type of group
All patients fulfilling eligibility criteria will enter the Induction Period, where they will receive 3 cycles of
standard first-line platinum doublet chemotherapy per investigator choice (carboplatin/paclitaxel,
cisplatin/gemcitabine or carboplatin/gemcitabine) until the end of the Induction Period or documented disease progression.
Group name:Treatment Period Type of group
• Category 1: Patients with a CR, PR or SD after 3 cycles of platinum induction chemotherapy. Patients with a CR, PR or SD during the Induction Period will be randomized
in a 3:1 ratio to receive either molecularly-guided therapy or to continuation of the same chemotherapy regimen used during induction, respectively.
• Category 2: Patients with a documented PD during 3 cycles of platinum induction chemotherapy. Category 2 patients, i.e., PD after or during 3 cycles of platinum induction
Sponsors
None listed
Eligibility
Inclusion criteria
Inclusion criteria: •Signed Informed Consent Form •Able and willing to comply with the study protocol •Age ≥ 18 years at time of signing Informed Consent Form •Histologically-confirmed metastatic or advanced unresectable CUP diagnosed. •At least one lesion that is measurable according to RECIST v1.1 (Appendix 5) - If a fresh biopsy is needed during Screening, the biopsy procedure must not affect measurability of disease •Availability of a tumor FFPE block ≤ 3 months old at Screening that is sufficient and suitable (in quantity and quality) for generation of a comprehensive genomic profile using Foundation Medicine® tissue biopsy assay. •No prior systemic therapy for the treatment of CUP - Patients who have received prior surgery and/or radiotherapy (including radioembolization of tumor) are eligible. If prior radiotherapy, the measurable lesion(s) must not have been irradiated - The last dose of radiotherapy must be at least 4 weeks prior to the first dose of study treatment and the patient must have recovered to grade 1 or less from any toxicity of radiotherapy. •ECOG performance status of 0 or 1 •Life expectancy ≥ 12 weeks •Eligible for platinum-based doublet chemotherapy (according to the reference information for the intended doublet therapy) •Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to initiation of study treatment. See protocol for more detail.
Exclusion criteria
Exclusion criteria: •Squamous cell CUP •Patients with any of the specific non-CUP neoplasms identified in the ESMO CUP guidelines including: - Non-epithelial cancer - Extragonadal germ-cell tumor •Patients belonging to any of the following subsets of CUP with favorable prognoses. •Known presence of brain or spinal cord metastasis (including metastases that have been irradiated), as determined by CT or magnetic resonance imaging (MRI) evaluation during screening •History or known presence of leptomeningeal disease •Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12 mg/dL or corrected serum calcium 2.9mmol/L) •Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis •Known human immunodeficiency virus (HIV) infection •Positive for hepatitis C virus (HCV) antibody at screening •Positive for hepatitis B surface antigen (HBsAg) at screening •Active tuberculosis at screening •Active infections requiring intravenous antibiotics. •Significant cardiovascular disease •Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study. •Treatment with investigational therapy within 28 days or the equivalent of 5 half-lives (whichever is the longest) prior to initiation of study treatment •Known allergy or hypersensitivity to any component of the platinum-doublet chemotherapy •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 24 months after the last dose of treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:RECIST, v1.1 Measure:Progression-free survival (PFS1), defined in Category 1 patients as the time from randomization to the first occurrence of disease progression, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. Timepoints:From randomization to the first occurrence of disease progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:RECIST v1.1. Measure: Overall survival (OS), defined as the time from randomization to death from any cause  Overall response rate (ORR1), defined in Category 1 patients as the proportion of randomized patients who exhibit a CR or PR to molecularly-guided therapy on two consecutive occasions ≥ 4 weeks apart  Duration of clinical benefit (DCB1), defined in Category 1 patients as the time from the first occurrence of a CR, PR or SD after randomization until disease progression or death from any cause, whichever occurs first Responses will be determined by the investigator according to RECIST v1.1 Timepoints:Throughout study. | — |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Mexico, Norway, Poland, Serbia, Spain, Switzerland, Turkey, United Kindgdom
Contacts
Public ContactLizeth Perez
ROCHE FARMA (PERU) S.A.
Outcome results
None listed