Clinical trial NCT00698243: Study of Oral OSI-027 in Patients With Advanced Solid Tumors or Lymphoma
Official title: A Phase 1 Dose-escalation Study of Intermittent, Once Weekly, and Continuous Daily Oral OSI-027 Dosing in Patients With Advanced Solid Tumors or Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Any Solid Tumor or Lymphoma
Keywords: OSI-027
Solid tumor
Lymphoma
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2008-06-17
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the maximum tolerated dose (MTD) and to establish the recommended phase 2 dose of oral OSI-027 when administered via 3 schedules, namely, intermittent, weekly, and continuous in patients with advanced solid tumors or lymphoma, namely, intermittent, weekly, and continuous.

Detailed description: The study will open with Schedule 1 (S1, intermittent) with initiation of Schedule 2 (S2, weekly) and Schedule 3 (S3, continuous), which may occur in parallel after observation of clinically significant related dose limiting toxicity (DLT) in the S1 schedule. Dosing will be initiated on Day 1 with intermittent weekly dosing continuing for 21 days (1 Treatment Period). Expansion of Dose Escalation Cohorts may occur for S1 and S2 at the recommended phase 2 dose level(s) and a Biomarker Expansion Cohort may be opened in S1 and/or S2.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically documented malignancy (solid tumor or lymphoma)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
* Predicted life expectancy of at least 3 months
* Adequate hematopoietic and hepatic function, and normal renal function
* Fasting glucose \<7mmol/L at baseline
* Left ventricular ejection fracture (LVEF) by Multiple gated acquisition scan (MUGA)≥ 60%
* Practice effective contraceptive measures throughout study
* Verbal and written informed consent
* Prior therapy:

  * Chemotherapy, minimum of 3 weeks and recovered from any treatment-related toxicities (except for alopecia, and grade 1 neurotoxicity) prior to registration
  * Hormonal, discontinued prior to registration
  * Radiation, minimum of 21 days and recovered from toxic effects prior to registration
  * Surgery, provided wound healing has occurred

Exclusion Criteria:

* History of significant cardiac disease unless well controlled
* Discontinuation from prior therapy due to cardiac toxicity
* Active or uncontrolled infections
* Serious illness or medical condition that could interfere with study participation
* History of any psychiatric condition that might impair understanding or compliance
* Documented history of diabetes mellitus
* Pregnant or breastfeeding females
* Unstable symptomatic brain metastases, that require steroid or that have required radiation in the last 28 days
* Chronic systemic steroid use for cancer related condition
* History of allergic reactions
* Patients with cataract who are expected to undergo surgery within 6 months of registration
* Use of drugs causing QT interval prolongation within 14 days prior to dosing
* Patients with clinically significant electrolyte imbalances

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 21 days
Secondary outcomes:
measure: Safety profile of OSI-027
timeFrame: up to 5 years
measure: Pharmacokinetic profile of OSI-027
timeFrame: up to 23 days
measure: Preliminary pharmacodynamic relationship with OSI-027 systemic exposure
timeFrame: up to 23 days
measure: Preliminary antitumor activity of OSI-027
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Sutton
country: United Kingdom
facility: Royal Mardsen Hospital
state: Surrey
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Monitor
role: STUDY_DIRECTOR
References: