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

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma

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

Study Overview

• Status: Completed
• Conditions: Adrenocortical Carcinoma
• Intervention / Treatment: Drug: OSI-906; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital Department of Endocrinology
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • PMH - Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• France
  • Lille, France, 59037 cedex
    • CHRU Lille, Clinique Endocrinologique Marc Linquette
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13273 cedex 09
    • Institut Paoli-Calmettes
  • Paris, France, 75679 Cedex 14
    • Hôpital Cochin-Saint Vincent de Paul
  • Pessac, France, 33604 CEDEX
    • CHU Bordeaux - Hôpital Haut-Lévêque
  • Villejuif, France, 94805 cedex
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin
  • Munich, Germany, 80336
    • LMU München
  • Wuerzburg, Germany, 97080
    • Universitaets Klinikum Wuerzburg
• Italy
  • Orbassano, Italy, 10043
    • Università di Torino
  • Rome, Italy, 00168
    • Università Cattolica del Sacro Cuore
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Eindhoven, Netherlands, 5631 BM
    • Maxima Medisch Centrum (MMC)
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC Rotterdam
• Poland
  • Gliwice, Poland, 44-101
    • Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie Oddzial w Gliwicach
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St. James' University hospital
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden NHS Trust
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • TGen Clinical Research Service at Scottsdale Healthcare
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2200
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Medical School
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clinical Cancer Trials Services
  • Ohio
    • Columbus, Ohio, United States, 43202
      • Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6307
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: OSI-906; 150 mg twice daily	Drug: OSI-906; Administered orally; Other Names: linsitinib
Placebo Comparator: Arm B: Placebo; Matching placebo twice daily	Other: Placebo; Matching placebo administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival of single agent OSI-906 versus placebo	Time from date of randomization until time of documented death	33 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2009
• Primary Completion (Actual): July 11, 2012
• Study Completion (Actual): October 8, 2012

Study Registration Dates

• First Submitted: June 17, 2009
• First Submitted That Met QC Criteria: June 18, 2009
• First Posted (Estimated): June 19, 2009

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: OSI-906; ACC; Adrenocortical carcinoma; GALACCTIC; Insulin-like growth factor-1 receptor (IGF-1R)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Carcinoma; Adrenocortical Carcinoma
• Other Study ID Numbers: OSI-906-301; 2009-012820-97 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR