Patients who have benefited from cytotoxic chemotherapy. Patients will have either metastatic soft-tissue or bone sarcoma, with histological category (soft-tissue or bone) as one of the baseline stratification factors. Importantly, in this trial, bone sarcoma patients must have visceral metastatic disease (e.g., metastatic to lung or liver), or have achieved response of visceral metastasis. MedDRA version: 14.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ C
Conditions
Interventions
Product Name: Ridaforolimus
Product Code: AP23573
Pharmaceutical Form: Tablet
INN or Proposed INN: ridaforolimus
CAS Number: 572924-54-0
Current Sponsor code: AP23573
Other descriptive name: MK-8669
C
Sponsors
Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Documented histologic diagnosis of soft-tissue or bone sarcoma that has metastasized, with the exception of certain histopathologic subtypes of sarcomas recognized by experts to derive no benefit from conventional chemotherapies or with distinctly different natural histories. See Attachment G for a list of excluded sarcoma sub-types. 2. Ongoing complete response, partial response or stable disease as defined by RECIST guidelines after a minimum of 4 cycles (and maximum of 12 months) of any one of 1st, 2nd or 3rd line of prior cytotoxic chemotherapy for metastatic disease. 3. Disease status (SD or better response) confirmed by a central review of at least the 2 most recent radiological evaluations (e.g., CT or MRI scans) obtained a minimum of 6 (± 1 week) and a maximum of 12 weeks (± 1 week) apart. 4. Patients with partial response or stable disease at study entry must have least one measurable or evaluable lesion as defined by RECIST guidelines (see protocol Attachment D) 5. Patients with only bone metastases are excluded. 6. ECOG performance status of 0 or 1 (see protocol Attachment A) 7. Male or female patients = 13 years of age (patients 13-17 years of age must weigh at least 100lbs. (45.4 kg)). In regions where applicable local law prohibits enrollment of patients 3 months Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 549 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or lactating 2. Presence of known or active brain or CNS metastases, unless successfully treated (i.e., controlled for> 3 months) 3. Prior therapy with rapamycin or rapamycin analogs, including AP23573 4. Ongoing toxicity associated with prior anticancer therapy = Grade 2 (excluding alopecia) according NCI common terminology criteria 5. Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ) 6. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin) 7. Concomitant treatment with medications that induce or inhibit CYP3A. Patients should be off these medications = 2 weeks prior to the first dose of AP23573 8. Significant uncontrolled cardiovascular disease 9. Active infection requiring systemic therapy 10. Known HIV infection 11. Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for = 2 weeks prior to first planned dose of study drug 12. 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) 13. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) of patients who have achieved complete response, partial response or stable disease following first, second or third line chemotherapy when treated with AP23573 versus placebo.;Secondary Objective: 1. To compare the overall survival (OS) of patients when treated with AP23573 versus placebo. 2. To compare the best target lesion response of patients receiving AP23573 versus placebo. 3. To assess changes in cancer-related symptoms in those patients treated with AP23573 compared to those treated with placebo. 4. To determine the safety and tolerability of AP23573. ;Primary end point(s): Progression-free survival, defined as the time from the date of randomization to the date of documented progressive disease, recurrence or death (whichever occurs first);Timepoint(s) of evaluation of this end point: Every 8 weeks until progressive disease is documented or another anticancer therapy is instituted, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (1) Overall survival defined as the time from the date of randomization to the date of death; (2) best target lesion response, defined as best change in sum of the target lesions from baseline to disease progression; (3) changes in select cancerrelated symptoms; and (4) safety and tolerability.;Timepoint(s) of evaluation of this end point: (1) Overall survival will be assessed at 3-month intervals after discontinuation; (2) best target lesion response will be assessed every 8 weeks until progressive disease is documented or another anti-cancer therapy is instituted, whichever occurs first; (3) cancer-related symptoms will be assessed every 4 weeks while on treatment; and (4) safety and tolerability will be assessed at each visit. | — |
Countries
Australia, Brazil, Canada, Chile, Czech Republic, France, Germany, Greece, India, Israel, Italy, Korea, Democratic People's Republic of, Mexico, Netherlands, New Zealand, Peru, Poland, Slovakia, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co, Inc.
Outcome results
None listed