Clinical trial NCT00924989: A Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adrenocortical Carcinoma
Keywords: Adrenocortical carcinoma
OSI-906
ACC
GALACCTIC
Insulin-like growth factor-1 receptor (IGF-1R)
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2009-06-19
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of single-agent OSI-906 in patients with locally advanced/metastatic Adrenocortical Carcinoma (ACC) who received at least 1 but no more than 2 prior drug regimens

Detailed description: Patients will be randomized 2:1 to receive either single agent OSI-906 (Arm A) or placebo (Arm B) and will be stratified according to prior systemic cytotoxic chemotherapy for ACC, and Eastern Cooperative Oncology Group (ECOG) performance status, and use of \>= 1 oral antihyperglycemic therapy at randomization

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adrenocortical carcinoma that is locally advanced or metastatic and not amenable to surgical resection.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) \<= 2
* Predicted life expectancy \>= 12 weeks.
* At least 1 but no more than 2 prior drug regimens (including molecular targeted therapy, systemic cytotoxic chemotherapy, biologics, and/or vaccines) for locally advanced/metastatic ACC.
* A minimum of 3 weeks must have elapsed between the end of prior treatment and randomization.
* All patients must have received prior mitotane, either as neoadjuvant, adjuvant, or locally advanced/metastatic therapy.
* Adjuvant and neoadjuvant mitotane therapy will not be counted as prior drug regimens or as systemic cytotoxic chemotherapy.
* Prior radiation therapy is permitted provided patients have recovered from the acute, toxic effects of radiotherapy prior to randomization.
* A minimum of 21 days must have elapsed between the end of radiotherapy and randomization.
* Prior surgery is permitted provided that adequate wound healing has occurred prior to randomization.
* Fasting glucose \< = 150 mg/dL (8.3 mmol/L).
* Adequate hematopoietic, hepatic, and renal function defined as follows: Neutrophil count \>= 1.5 x 10\^9 /L;
* Platelet count \>= 100 x 10\^9 /L;
* Bilirubin \<= 1.5 x Upper Limit of Normal (ULN);
* AST and ALT \<= 2.5 x ULN, or \<= 5 x ULN if patient has documented liver metastases or received prior mitotane therapy; and
* Serum creatinine \<= 1.5 x ULN or \<= 2.0 x ULN if the patient has received prior cisplatin.
* Patients, both males and females, with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must agree to practice effective contraceptive measures throughout the study.
* Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to randomization.
* Patients must provide verbal and written informed consent to participate in the study.
* Radiologically-confirmed progressive disease within 6 months prior to randomization.
* Concurrent use of non-insulinotropic oral antihyperglycemic therapy is permitted if the dose has been stable for \>= 4 weeks at the time of randomization.

Exclusion Criteria:

* Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy.
* Prior IGF-1R inhibitor therapy.
* Malignancy other than ACC within the past 3 years. Exceptions: resected basal cell or squamous cell carcinoma of the skin; cured in situ cervical carcinoma; cured ductal carcinoma in situ of the breast; and/or cured superficial bladder cancer.
* History of significant cardiovascular disease unless the disease is well-controlled.
* Significant cardiac diseases includes second/third degree heart block; clinically significant ischemic heart disease; mean QTcF interval \> 450 msec at screening;
* poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea).
* History of cerebrovascular accident (CVA) within 6 months prior to randomization or that resulted in ongoing neurologic instability.
* Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing.
* Active infection or serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization) that would impair the ability of the patient to receive study drug.
* History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
* Pregnant or breast-feeding females.
* Symptomatic brain metastases that are not stable, require steroids, are potentially life threatening, or that have required radiation within 28 days prior to randomization.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug.

Primary outcomes:
measure: Overall survival of single agent OSI-906 versus placebo
timeFrame: 33 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 24 months
measure: Disease control rate
timeFrame: 24 months
measure: Best overall response rate
timeFrame: 24 months
measure: Duration of response
timeFrame: 24 months
measure: Time to deterioration in Quality of Life
timeFrame: 24 months
measure: Safety assessed via physical exams, vital signs, laboratory assessments, electrocardiograms, and adverse events
timeFrame: 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGen Clinical Research Service at Scottsdale Healthcare
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: University of Colorado Denver Cancer Center
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Medical School
state: New Hampshire
city: Durham
country: United States
facility: Duke Clinical Cancer Trials Services
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: St Leonards
country: Australia
facility: Royal North Shore Hospital Department of Endocrinology
state: New South Wales
city: Hamilton
country: Canada
facility: St. Joseph's Hospital
state: Ontario
city: Toronto
country: Canada
facility: PMH - Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Lille
country: France
facility: CHRU Lille, Clinique Endocrinologique Marc Linquette
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Paris
country: France
facility: Hôpital Cochin-Saint Vincent de Paul
city: Pessac
country: France
facility: CHU Bordeaux - Hôpital Haut-Lévêque
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin
city: Munich
country: Germany
facility: LMU München
city: Wuerzburg
country: Germany
facility: Universitaets Klinikum Wuerzburg
city: Orbassano
country: Italy
facility: Universita di Torino
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum (MMC)
city: Rotterdam
country: Netherlands
facility: Erasmus MC Rotterdam
city: Gliwice
country: Poland
facility: Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie Oddzial w Gliwicach
city: Leeds
country: United Kingdom
facility: St. James' University hospital
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Fassnacht M, Berruti A, Baudin E, Demeure MJ, Gilbert J, Haak H, Kroiss M, Quinn DI, Hesseltine E, Ronchi CL, Terzolo M, Choueiri TK, Poondru S, Fleege T, Rorig R, Chen J, Stephens AW, Worden F, Hammer GD. Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study. Lancet Oncol. 2015 Apr;16(4):426-35. doi: 10.1016/S1470-2045(15)70081-1. Epub 2015 Mar 18.