Clinical trial NCT00819221: AZD2281 in Combination With Liposomal Doxorubicin in Advanced Solid Tumours
Official title: A Phase I, Open Label, Multicenter Study to Assess the Safety, Tolerability and Pharmacology of AZD2281 in Combination With Liposomal Doxorubicin (Caelyx®) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: advanced tumors
solid tumors
dose escalation
combination
AZD2281
liposomal doxorubicin
pharmacology
phase I
multicenter
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-01-08
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will be an open label, multicenter, dose finding study. Depending on the tolerated dose up to 7 dose levels will be explored in this study, approximately 33 patients (21-54 depending on number of cohorts) may be enrolled into this study. Three patients will be initially dosed in each cohort. The primary objective of this study is to determine the recommended dose (RD) of twice daily oral doses of AZD2281 either as intermittent therapy for 7 days out of a 28-day schedule or given continuously, administered in combination with liposomal doxorubicin to patients with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed metastatic cancer, not amenable to surgery or radiation therapy with curative intent
* Measurable or evaluable disease
* ECOG Performance status 0 - 2
* Estimated life expectancy of at least 12 weeks

Exclusion Criteria:

* More than 3 prior lines of chemotherapy for advanced disease
* Less than 28 days from active treatment (ie, any treatment used to treat the disease) or high dose radiotherapy (patients may continue concomitant use of stable dose of bisphosphonates if used at least 28 days prior to commencing study treatment and pat
* Prior treatment with \>300mg/m2 cumulative dose of doxorubicin equivalent
* Resistance to anthracyclines defined as progressive disease during anthracycline treatment or within 6 months after the last anthracycline administration.

Primary outcomes:
measure: recommended dose
timeFrame: 2 months
Secondary outcomes:
measure: pharmacokinetics
timeFrame: 6 visits within 1 month
measure: safety/tolerability/toxicity
timeFrame: 2 months
measure: DNA repair mechanism
timeFrame: once
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Research Site
city: Bellinzona
country: Switzerland
facility: Research Site
city: Chur
country: Switzerland
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Jane Robertson, BSc, MBCHB, MD
role: STUDY_DIRECTOR
References:
citation: Del Conte G, Sessa C, von Moos R, Vigano L, Digena T, Locatelli A, Gallerani E, Fasolo A, Tessari A, Cathomas R, Gianni L. Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. Br J Cancer. 2014 Aug 12;111(4):651-9. doi: 10.1038/bjc.2014.345. Epub 2014 Jul 15.