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

Sponsor

Astellas Pharma Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00924989

Collaborator

(none)

139

Enrollment

Locations

Arms

34.2

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Adrenocortical Carcinoma	Drug: OSI-906 Other: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

139 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Jul 11, 2012

Actual Study Completion Date :

Oct 8, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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