Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000214336
Ethics application status
Approved
Date submitted
17/04/2008
Date registered
18/04/2008
Date last updated
3/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Pivotal Trial to Determine the Efficacy and Safety of AP23573 when Administered as Maintenance Therapy to Patients with Metastatic Soft Tissue or Bone Sarcomas.
Scientific title
A Phase 3, Randomised, Multi-Centre, Double Blinded, Placebo Controlled Trial to Determine the Efficacy and Safety of Oral AP23573 Versus Oral Placebo in Patients with Metastatic Sarcoma when Administered as Maintenance Therapy.
Secondary ID [1] 544 0
EudraCT number: 2007-003462-18
Secondary ID [2] 545 0
IND Reference Number:72,003
Secondary ID [3] 546 0
ClinicalTrials.gov: NCT00538239
Secondary ID [4] 547 0
Protocol number: AP23573-07-302
Universal Trial Number (UTN)
Trial acronym
SUCCEED
Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Deforolimus
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic soft tissue or bone sarcomas 3072 0
Condition category
Condition code
Cancer 3227 3227 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 3228 3228 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi-centre, randomised Phase 3, double-blinded, placebo-controlled trial to determine the efficacy and safety of oral AP23573 (MK-8669) versus oral placebo in patients with metastatic sarcoma. Eligible patients include those with metastatic soft-tissue or bone sarcoma who have achieved a complete response, partial response or stable disease following 1st, 2nd or 3rd line chemotherapy for metastatic sarcoma. The trial is designed to test the hypothesis that a clinically significant improvement in progression-free survival will be induced in patients treated with AP23573 compared to placebo. It is anticipated that approximately 650 patients, age from 13 years will participate in this trial. AP23573 will be administered once daily as oral tablets for 5 consecutive days followed by a 2-day dosing holiday each week at a dose of 40 mg per day. Patients randomised to the placebo arm will receive matched tablets consisting of excipients without active drug

Patients must have achieved an ongoing complete response, partial response or stable disease following prior therapy as defined by Response Evaluation Criteria in Solid Tumours (RECIST) guidelines. The disease status at study entry will be confirmed through an independent radiographic review during the screening period (prior to randomisation). Only eligible patients will be randomized. Patients will be randomly assigned (1:1) to receive either AP23573 or placebo by oral administration. Treatment will continue until progressive disease by RECIST guidelines is documented or other discontinuation criteria are met. Patients will be stratified by geographical region, histological category (soft-tissue or bone sarcoma), and prior treatment (1st line or 2nd/3rd line). Disease assessments will be performed every 8 weeks and assessed in accordance with the RECIST guidelines. Patients will be followed for overall survival for at least 24 months and up to 60 months following randomisation.
Intervention code [1] 2814 0
Treatment: Drugs
Comparator / control treatment
Oral placebo tablets matched to the characteristics (size, colour, and excipients) of the AP23573 tablets
Control group
Placebo

Outcomes
Primary outcome [1] 4110 0
Progression-free Survival
Timepoint [1] 4110 0
This is assessed every 8 weeks for at least 24 months and up to 60 months following randomisation
Secondary outcome [1] 6924 0
Overall survival, antitumor response, change in cancer-related symptoms, safety, and tolerability.
Timepoint [1] 6924 0
This is assessed every 8 weeks for at least 24 months and up to 60 months following randomisation

Eligibility
Key inclusion criteria
Inclusion Criteria:
• Confirmed diagnosis of metastatic soft-tissue or bone sarcoma
• Ongoing favorable outcome after a minimum of 4 cycles of prior chemotherapy for metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Age from 13 years (patients 13-17 years of age must weigh at least 100lbs/45.4kgs)
• Adequate organ and bone marrow function
• Completed prior chemotherapy with last dose received at least 3 and up to 8 weeks prior to randomization
Minimum age
13 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Women who are pregnant or lactating
• Presence of known or active brain or CNS (Central Nervous System) metastases
• Prior therapy with rapamycin or rapamycin analogs, including AP23573
• Ongoing toxicity associated with prior anticancer therapy greater than or equal to Grade 2 (excluding alopecia) according to NCI (National Cancer institute - of the US) common terminology criteria
• Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ)
• Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
• Concomitant treatment with medications that induce or inhibit CYP3A. Patients should be off these medications greater than or equal to 2 weeks prior to the first dose of AP23573
• Significant uncontrolled cardiovascular disease
• Active infection requiring systemic therapy
• Known HIV (Human Immunodeficiency Virus) infection
• Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for greater than or equal to 2 weeks prior to first planned dose of study drug
• Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of study drug (with the exception of minor procedures, e.g., central venous access port placement)
• Presence of any life-threatening illness or organ system dysfunction which, in the option of the Investigator, would either compromise the patient’s safety or interfere with evaluating the safety of the study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
650
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,SA,WA
Recruitment postcode(s) [1] 645 0
2031
Recruitment postcode(s) [2] 646 0
2050
Recruitment postcode(s) [3] 823 0
2606
Recruitment postcode(s) [4] 825 0
3052
Recruitment postcode(s) [5] 647 0
5035
Recruitment postcode(s) [6] 824 0
6000
Recruitment outside Australia
Country [1] 925 0
United States of America
State/province [1] 925 0
Country [2] 926 0
Canada
State/province [2] 926 0
Country [3] 927 0
Belgium
State/province [3] 927 0
Country [4] 928 0
Czech Republic
State/province [4] 928 0
Country [5] 929 0
France
State/province [5] 929 0
Country [6] 930 0
Germany
State/province [6] 930 0
Country [7] 931 0
Greece
State/province [7] 931 0
Country [8] 932 0
Israel
State/province [8] 932 0
Country [9] 933 0
Netherlands
State/province [9] 933 0
Country [10] 934 0
Poland
State/province [10] 934 0
Country [11] 935 0
Romania
State/province [11] 935 0
Country [12] 936 0
Slovakia
State/province [12] 936 0
Country [13] 937 0
Spain
State/province [13] 937 0
Country [14] 938 0
Sweden
State/province [14] 938 0
Country [15] 939 0
United Kingdom
State/province [15] 939 0
Country [16] 940 0
India
State/province [16] 940 0
Country [17] 941 0
Korea, Democratic People's Republic Of
State/province [17] 941 0
Country [18] 942 0
New Zealand
State/province [18] 942 0
Country [19] 943 0
Argentina
State/province [19] 943 0
Country [20] 944 0
Colombia
State/province [20] 944 0
Country [21] 945 0
Mexico
State/province [21] 945 0
Country [22] 946 0
Peru
State/province [22] 946 0
Country [23] 947 0
Chile
State/province [23] 947 0
Country [24] 948 0
South Africa
State/province [24] 948 0
Country [25] 949 0
Brazil
State/province [25] 949 0
Country [26] 950 0
Italy
State/province [26] 950 0

Funding & Sponsors
Funding source category [1] 3321 0
Commercial sector/Industry
Name [1] 3321 0
ARIAD Pharmaceuticals, Inc.
Country [1] 3321 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
ARIAD Pharmaceuticals, Inc.
Address
26 Landsdowne Street
Cambridge, MA 02139-4234
Telephone: (617) 494-0400
Country
United States of America
Secondary sponsor category [1] 2969 0
None
Name [1] 2969 0
Address [1] 2969 0
Country [1] 2969 0
Other collaborator category [1] 268 0
Commercial sector/Industry
Name [1] 268 0
Merck Sharpe and Dohme
Address [1] 268 0
54-68 Ferndell Street,
South Granville NSW 2142
Country [1] 268 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5303 0
Ethics committee address [1] 5303 0
50 sites
Ethics committee country [1] 5303 0
United States of America
Date submitted for ethics approval [1] 5303 0
Approval date [1] 5303 0
13/08/2007
Ethics approval number [1] 5303 0
Ethics committee name [2] 5304 0
Ethics committee address [2] 5304 0
6 sites - approval pending
Ethics committee country [2] 5304 0
Canada
Date submitted for ethics approval [2] 5304 0
Approval date [2] 5304 0
Ethics approval number [2] 5304 0
Ethics committee name [3] 5305 0
Ethics committee address [3] 5305 0
2 sites - approval pending
Ethics committee country [3] 5305 0
Belgium
Date submitted for ethics approval [3] 5305 0
Approval date [3] 5305 0
Ethics approval number [3] 5305 0
Ethics committee name [4] 5306 0
Ethics committee address [4] 5306 0
2 sites
Ethics committee country [4] 5306 0
Czech Republic
Date submitted for ethics approval [4] 5306 0
Approval date [4] 5306 0
11/01/2008
Ethics approval number [4] 5306 0
Ethics committee name [5] 5307 0
Ethics committee address [5] 5307 0
7 sites
Ethics committee country [5] 5307 0
France
Date submitted for ethics approval [5] 5307 0
Approval date [5] 5307 0
25/01/2008
Ethics approval number [5] 5307 0
Ethics committee name [6] 5308 0
Ethics committee address [6] 5308 0
4 sites - approval pending
Ethics committee country [6] 5308 0
Germany
Date submitted for ethics approval [6] 5308 0
Approval date [6] 5308 0
Ethics approval number [6] 5308 0
Ethics committee name [7] 5309 0
Ethics committee address [7] 5309 0
2 sites - approval pending
Ethics committee country [7] 5309 0
Greece
Date submitted for ethics approval [7] 5309 0
Approval date [7] 5309 0
Ethics approval number [7] 5309 0
Ethics committee name [8] 5310 0
Ethics committee address [8] 5310 0
4 sites
Ethics committee country [8] 5310 0
Israel
Date submitted for ethics approval [8] 5310 0
Approval date [8] 5310 0
29/01/2008
Ethics approval number [8] 5310 0
Ethics committee name [9] 5311 0
Ethics committee address [9] 5311 0
8 sites
Ethics committee country [9] 5311 0
Italy
Date submitted for ethics approval [9] 5311 0
Approval date [9] 5311 0
23/01/2008
Ethics approval number [9] 5311 0
Ethics committee name [10] 5312 0
Ethics committee address [10] 5312 0
1 site - approval pending
Ethics committee country [10] 5312 0
Netherlands
Date submitted for ethics approval [10] 5312 0
Approval date [10] 5312 0
Ethics approval number [10] 5312 0
Ethics committee name [11] 5313 0
Ethics committee address [11] 5313 0
2 sites - approval pending
Ethics committee country [11] 5313 0
Poland
Date submitted for ethics approval [11] 5313 0
Approval date [11] 5313 0
Ethics approval number [11] 5313 0
Ethics committee name [12] 5314 0
Ethics committee address [12] 5314 0
6 sites - approval pending
Ethics committee country [12] 5314 0
Romania
Date submitted for ethics approval [12] 5314 0
Approval date [12] 5314 0
Ethics approval number [12] 5314 0
Ethics committee name [13] 5315 0
Ethics committee address [13] 5315 0
4 sites - approval pending
Ethics committee country [13] 5315 0
Slovakia
Date submitted for ethics approval [13] 5315 0
Approval date [13] 5315 0
Ethics approval number [13] 5315 0
Ethics committee name [14] 5316 0
Ethics committee address [14] 5316 0
6 sites
Ethics committee country [14] 5316 0
Spain
Date submitted for ethics approval [14] 5316 0
Approval date [14] 5316 0
05/02/2008
Ethics approval number [14] 5316 0
Ethics committee name [15] 5317 0
Ethics committee address [15] 5317 0
3 sites
Ethics committee country [15] 5317 0
Sweden
Date submitted for ethics approval [15] 5317 0
Approval date [15] 5317 0
22/01/2008
Ethics approval number [15] 5317 0
Ethics committee name [16] 5318 0
Ethics committee address [16] 5318 0
7 sites - approval pending
Ethics committee country [16] 5318 0
United Kingdom
Date submitted for ethics approval [16] 5318 0
Approval date [16] 5318 0
Ethics approval number [16] 5318 0
Ethics committee name [17] 5319 0
Ethics committee address [17] 5319 0
6 sites
Ethics committee country [17] 5319 0
Australia
Date submitted for ethics approval [17] 5319 0
Approval date [17] 5319 0
07/04/2008
Ethics approval number [17] 5319 0
Ethics committee name [18] 5320 0
Ethics committee address [18] 5320 0
9 sites
Ethics committee country [18] 5320 0
India
Date submitted for ethics approval [18] 5320 0
Approval date [18] 5320 0
24/01/2008
Ethics approval number [18] 5320 0
Ethics committee name [19] 5321 0
Ethics committee address [19] 5321 0
6 sites - approval pending
Ethics committee country [19] 5321 0
Korea, Democratic People's Republic Of
Date submitted for ethics approval [19] 5321 0
Approval date [19] 5321 0
Ethics approval number [19] 5321 0
Ethics committee name [20] 5322 0
Ethics committee address [20] 5322 0
4 sites - approval pending
Ethics committee country [20] 5322 0
New Zealand
Date submitted for ethics approval [20] 5322 0
Approval date [20] 5322 0
Ethics approval number [20] 5322 0
Ethics committee name [21] 5323 0
Ethics committee address [21] 5323 0
4 sites
Ethics committee country [21] 5323 0
Argentina
Date submitted for ethics approval [21] 5323 0
Approval date [21] 5323 0
06/12/2007
Ethics approval number [21] 5323 0
Ethics committee name [22] 5324 0
Ethics committee address [22] 5324 0
3 sites - approval pending
Ethics committee country [22] 5324 0
Brazil
Date submitted for ethics approval [22] 5324 0
Approval date [22] 5324 0
Ethics approval number [22] 5324 0
Ethics committee name [23] 5325 0
Ethics committee address [23] 5325 0
2 sites
Ethics committee country [23] 5325 0
Colombia
Date submitted for ethics approval [23] 5325 0
Approval date [23] 5325 0
30/01/2008
Ethics approval number [23] 5325 0
Ethics committee name [24] 5326 0
Ethics committee address [24] 5326 0
4 sites
Ethics committee country [24] 5326 0
Mexico
Date submitted for ethics approval [24] 5326 0
Approval date [24] 5326 0
18/12/2007
Ethics approval number [24] 5326 0
Ethics committee name [25] 5327 0
Ethics committee address [25] 5327 0
3 sites - approval pending
Ethics committee country [25] 5327 0
Peru
Date submitted for ethics approval [25] 5327 0
Approval date [25] 5327 0
Ethics approval number [25] 5327 0
Ethics committee name [26] 5328 0
Ethics committee address [26] 5328 0
3 sites - approval pending
Ethics committee country [26] 5328 0
Chile
Date submitted for ethics approval [26] 5328 0
Approval date [26] 5328 0
Ethics approval number [26] 5328 0
Ethics committee name [27] 5329 0
Ethics committee address [27] 5329 0
4 sites
Ethics committee country [27] 5329 0
South Africa
Date submitted for ethics approval [27] 5329 0
Approval date [27] 5329 0
16/01/2008
Ethics approval number [27] 5329 0

Summary
Brief summary
Phase 3
This is a pivotal study to determine the effectiveness and safety of AP23573 (deforolimus) when administered as maintenance therapy to people with metastatic cancers of either soft tissue or bone.

Who is it for?
This trial is for you is you have metastatic cancers of either soft tissue or bone connective tissue, and have already had your cancer controlled by chemotherapy.

Trial Details
Participants will be randomly divided into two groups. One group will receive maintenance treatment with oral AP23573 (deforolimus) and the other will receive standard treatment. The trial aims to see whether those people receiving oral AP23573 (deforolimus) have better disease control compared to those receiving standard treatment. Deforolimus has shown promising activity in early phase trials and its side effects are generally mild and reversible and include mouth sores, fatigue and nausea.’
Deforolimus inhibits the protein mTOR, which is a ‘master switch’ in cancer cells. Blocking mTOR effectively ‘starves’ cancer cells by interfering with cell growth, division, metabolism, and blood vessel growth. If you have metastatic cancers of either soft tissue or bone connective tissue, you usually receive chemotherapy until the disease is controlled or until chemotherapy causes significant side effects. Chemotherapy is then stopped and your cancer specialist observes you regularly. This trial is testing whether, once the disease has been controlled with chemotherapy, treatment with oral AP23573 (deforolimus) can control the cancer for longer compared to standard treatment.
Trial website
www.succeedtrial.com
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 28542 0
Address 28542 0
Country 28542 0
Phone 28542 0
Fax 28542 0
Email 28542 0
Contact person for public queries
Name 11699 0
Jeanette Lodge
Address 11699 0
156-158 Drummond St
Oakleigh VIC 3166
Country 11699 0
Australia
Phone 11699 0
+ 61 3 9877 7613
Fax 11699 0
+ 61 3 9567 7699
Email 11699 0
Lodge.jeanette@kendle.com
Contact person for scientific queries
Name 2627 0
Ric DeGaris
Address 2627 0
156-158 Drummond St
Oakleigh VIC 3166
Country 2627 0
Australia
Phone 2627 0
+ 61 3 9877 7602
Fax 2627 0
+ 61 3 9567 7699
Email 2627 0
degaris.ric@kendle.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.