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

Phase 3

Completed

• Conditions: Adrenocortical Carcinoma
• Interventions: Drug: OSI-906; Other: Placebo

• Registration Number: NCT00924989
• Lead Sponsor: Astellas Pharma Inc

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

Study Timeline

• Study First Submitted: 2009-06-17
• Study First Submitted QC: 2009-06-18
• Study First Posted: 2009-06-19
• Study Start: 2009-12-01
• Primary Completion: 2012-07-11
• Study Completion: 2012-10-08
• Disposition First Submitted: 2013-07-10
• Disposition First Submitted QC: 2013-07-10
• Disposition First Posted: 2013-07-12
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 139

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: OSI-906	OSI-906	150 mg twice daily
Arm B: Placebo	Placebo	Matching placebo twice daily

Primary Outcome Measures

Name	Time	Method
Overall survival of single agent OSI-906 versus placebo	33 months	Time from date of randomization until time of documented death

Secondary Outcome Measures

Name	Time	Method
Time to deterioration in Quality of Life	24 months	Measured by European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires
Safety assessed via physical exams, vital signs, laboratory assessments, electrocardiograms, and adverse events	24 months
Progression-free survival	24 months	Time from randomization to disease progression based on RECIST version 1.1 or death due to any cause, whichever comes first
Disease control rate	24 months	Proportion of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD), based on RECIST criteria
Best overall response rate	24 months	Proportion of patients with a best overall response of CR or PR based on RECIST criteria
Duration of response	24 months	Time from date of the first documented response (CP/PR) to documented progression or death due to underlying cancer

Trial Locations

Locations (35)

Mary Crowley Cancer Research Center; 🇺🇸 Dallas, Texas, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Centre hospitalier de l'Université de Montréal (CHUM); 🇨🇦 Montreal, Quebec, Canada

University of Colorado Denver Cancer Center; 🇺🇸 Aurora, Colorado, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Charite Universitaetsmedizin; 🇩🇪 Berlin, Germany

TGen Clinical Research Service at Scottsdale Healthcare; 🇺🇸 Scottsdale, Arizona, United States

UCLA; 🇺🇸 Los Angeles, California, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Dartmouth Medical School; 🇺🇸 Lebanon, New Hampshire, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

St. Joseph's Hospital; 🇨🇦 Hamilton, Ontario, Canada

Royal North Shore Hospital Department of Endocrinology; 🇦🇺 St Leonards, New South Wales, Australia

Centre Léon Bérard; 🇫🇷 Lyon, France

PMH - Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

CHRU Lille, Clinique Endocrinologique Marc Linquette; 🇫🇷 Lille, France

Hôpital Cochin-Saint Vincent de Paul; 🇫🇷 Paris, France

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

CHU Bordeaux - Hôpital Haut-Lévêque; 🇫🇷 Pessac, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

LMU München; 🇩🇪 Munich, Germany

Università Cattolica del Sacro Cuore; 🇮🇹 Rome, Italy

Universitaets Klinikum Wuerzburg; 🇩🇪 Wuerzburg, Germany

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

Universita di Torino; 🇮🇹 Orbassano, Italy

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

University of Southern California; 🇺🇸 Los Angeles, California, United States

Duke Clinical Cancer Trials Services; 🇺🇸 Durham, North Carolina, United States