A Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma

NCT ID: NCT00924989

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-01
• Study Completion Date: 2012-10-08

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

Conditions

Adrenocortical Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A: OSI-906

150 mg twice daily

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

Administered orally

Arm B: Placebo

Matching placebo twice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo administered orally

Interventions

OSI-906

Administered orally

Intervention Type: DRUG

Placebo

Matching placebo administered orally

Intervention Type: OTHER

Other Intervention Names

linsitinib

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development

Locations

TGen Clinical Research Service at Scottsdale Healthcare

Scottsdale, Arizona, United States

University of Southern California

Los Angeles, California, United States

UCLA

Los Angeles, California, United States

University of Colorado Denver Cancer Center

Aurora, Colorado, United States

University of Miami

Miami, Florida, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Dartmouth Medical School

Lebanon, New Hampshire, United States

Duke Clinical Cancer Trials Services

Durham, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Royal North Shore Hospital Department of Endocrinology

St Leonards, New South Wales, Australia

St. Joseph's Hospital

Hamilton, Ontario, Canada

PMH - Princess Margaret Hospital

Toronto, Ontario, Canada

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

CHRU Lille, Clinique Endocrinologique Marc Linquette

Lille, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli-Calmettes

Marseille, , France

Hôpital Cochin-Saint Vincent de Paul

Paris, , France

CHU Bordeaux - Hôpital Haut-Lévêque

Pessac, , France

Institut Gustave Roussy

Villejuif, , France

Charite Universitaetsmedizin

Berlin, , Germany

LMU München

Munich, , Germany

Universitaets Klinikum Wuerzburg

Würzburg, , Germany

Universita di Torino

Orbassano, , Italy

Università Cattolica del Sacro Cuore

Rome, , Italy

Academic Medical Center

Amsterdam, , Netherlands

Maxima Medisch Centrum (MMC)

Eindhoven, , Netherlands

Erasmus MC Rotterdam

Rotterdam, , Netherlands

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie Oddzial w Gliwicach

Gliwice, , Poland

St. James' University hospital

Leeds, , United Kingdom

Royal Marsden NHS Trust

London, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Italy; Netherlands; Poland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 25795408 (View on PubMed)

Related Links

https://astellasclinicalstudyresults.com/study.aspx?ID=230

Link to results on the Astellas Clinical Study Results website.

Other Identifiers

2009-012820-97

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OSI-906-301

Identifier Type: -

Identifier Source: org_study_id