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.
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.
ARIAD Pharmaceuticals, Inc.
650 participants
Sep 1, 2007
Interventional
Conditions
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.
Eligibility
Inclusion Criteria6
- 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
Exclusion Criteria13
- 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
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Interventions
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.
Locations(26)
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ACTRN12608000214336