A Phase II Study of AP23573, an mTOR Inhibitor, in Patients with Advanced Sarcoma

Phase 1

• Conditions: Metastatic and/or unresectable soft tissue or bone sarcoma (excluding GIST).

• Registration Number: EUCTR2004-002231-92-BE
• Lead Sponsor: ARIAD Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-04
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 176

Inclusion Criteria

1.Patients =15 years of age with metastatic and/or unresectable sarcomas of the following histological subgroups:
·Bone sarcomas, such as osteosarcoma and Ewings sarcoma
·Leiomyosarcoma
·Liposarcomas*
·Any other soft tissue sarcoma* except GIST
* Patients with well-differentiated liposarcoma or desmoid tumors must have demonstrated progressive disease within the previous 6 months.
2.Presence of at least one measurable lesion that:
·Can be accurately measured in at least one dimension with longest diameter =20 mm using conventional techniques or =10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans).
·Previously irradiated lesions may be considered to be measurable provided: 1) there has been documented progression of the lesion(s) since completion of radiotherapy, and 2) the criteria for measurability as outlined above are met.
3.ECOG performance status =1
4.Minimum life expectancy of 3 months
5.Adequate renal and hepatic function, defined as:
·Total serum bilirubin = 1.5 x ULN for the institution
·AST and/or ALT = 3 x ULN for the institution (= 5 x ULN if liver metastases are present)
·Serum albumin = 2.5 g/dL
·Serum Creatinine =1.5 x ULN for the institution (or a calculated creatinine clearance = 50 mL/min/1.73m2)
6.Adequate bone marrow function, defined as:
·ANC = 1.5 x 10^9/L
·Platelet count = 100 x 10^9/L
7.Serum cholesterol <350 mg/dL and triglycerides < 400 mg/dL
8.Male and female patients who are not surgically sterile or postmenopausal must agree to use reliable methods of birth control for the duration of the study until 30 days after the last dose of study drug
9.Able to understand and give written informed consent

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Women who are pregnant or lactating
2.Presence of brain metastases
3.Prior therapy with rapamycin, rapamycin analogues or tacrolimus
4.Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biologoical response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of AP23573; the interval is = 2 weeks for signal transduction inhibitors with a half-life known to be <24 hours, and is = 6 weeks for nitrosourea or mitomycin. The following exceptions are allowed:
·hormonal therapy (e.g., Megace) for appetite stimulation
·nasal, ophthalmic, and topical glucocorticoid preparations
·a stable dose of corticosteroids for at least two weeks
·low dose maintenance steroid therapy for other conditions
·physiologic hormone replacement therapy (e.g., thyroid supplementation for thyroid deficiency or oral replacement glucocorticoid therapy for adrenal insufficiency)
5.Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of = grade 1 by NCI toxicity criteria)
6.Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ)
7.Known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug
8.Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
9.Significant uncontrolled cardiovascular disease
10.Active infection requiring systemic therapy
11.Known HIV infection
12.Treatment with any investigational agent within 4 weeks prior to the first dose of AP23573
13.Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for = 2 weeks prior to first planned dose of study drug
14.Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of AP23573
·Patients having undergone recent placement of a central venous access port will be considered eligible if they have recovered
15.Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient’s safety or interfere with evaluating the safety of the study drug

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assess the efficacy of AP23573 in patients with advanced sarcoma when administered once daily for 5 consecutive days every two weeks (QDx5).;Secondary Objective: Assess safety and tolerability of this study drug regimen.<br><br>Evaluate secondary efficacy endpoints, such as time to tumor progression, progression-free survival and duration of response.<br><br>Examine AP23573 blood levels and experimental parameters that may predict or indicate response to mTOR inhibition, such as effects on plasma VEGF levels and markers or tumoral PI3K/mTOR-pathway activity.;Primary end point(s): Complete or partial response or prolonged stable disease = 16 weeks duration, as assessed using modified RECIST guidelines.