Metastatic or Locally Advanced Chondrosarcoma MedDRA version: 14.1 Level: PT Classification code 10008734 Term: Chondrosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: IPI-926
Product Code: IPI-926
Pharmaceutical Form: Capsule
INN or Proposed INN: Not available yet
Current Sponsor code: IPI-926
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Infinity Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years of age at the time of signing informed consent. 2. Pathologically diagnosed conventional chondrosarcoma. (Note: Patients must have tumor sample(s) available or provide tumor samples from a new biopsy for central confirmation of diagnosis. Central pathology review will be completed after randomization. The most recent tumor tissue sample will be used for diagnosis.) Note: Please carefully ensure that the pathology indicates conventional chondrosarcoma. Less common subtypes such as dedifferentiated, mesenchymal, and clear cell chondrosarcomas are NOT conventional chondrosarcoma. Please be aware that "extraskeletal myxoid chondrosarcoma" is not truly a chondrosarcoma (despite the retention of this historical term by pathologists and oncologists) and patients with this pathology are NOT eligible for the study. 3. Metastasis to at least 1 location or locally advanced disease that is deemed unresectable by a surgeon. 4. At least 1 radiologically measurable target lesion per RECIST 1.1. If the lesion has received prior radiotherapy, then progression of the lesion (defined as radiographic growth of the lesion by at least 20%) must have occurred since the completion of radiation. 5. Patients must have documented radiographic progression of disease within the 6-month period prior to screening. Note: RECIST-defined radiographic progression of disease will be based on at least two sets of scans (either MRI or CT) taken during the period of time from 6 months prior to the date of signing study consent through the start of study drug dosing. The second of these two scans may be the baseline scan. Central review of eligibility scans will be performed. 6. Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1. 7. Life expectancy of at least 3 months. 8. Recovery to = Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia. 9. All women of child-bearing potential (WCBP), all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study and for 30 days after the last dose of study drug. Women of child-bearing potential (defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months for women =55 years, for women >55 years 12 consecutive months) must have a negative serum or urine ß human chorionic gonadotropin (ßhCG) pregnancy test. Adequate methods of contraception include use of oral contraceptives or Depo-Provera, with an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence. 10. Ability to adhere to the study visit schedule and all protocol requirements. 11. Voluntarily signed an informed consent form. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 112 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Other invasive malignancies diagnose within the last 5 years, except non melanoma skin cancer and localized cured prostate and cervical cancer. 2. Systemic anti-cancer therapy within 21 days prior to the first dose of study drug, or radiotherapy within 14 days prior to the first dose of study drug. 3. Prior treatment with a Hedgehog pathway inhibitor. 4. Medically significant surgical procedures or significant traumatic injury within 28 days before Day 1. 5. Inadequate hematologic function defined by: • Hemoglobin 2.5 x upper limit of normal (ULN). • Total bilirubin >1.5 x ULN (with the exception of patients with Gilbert’s disease). • Cirrhotic liver disease, ongoing alcohol abuse, or known chronic active or acute hepatitis. 7. Inadequate renal function defined by serum creatinine >1.5 x ULN. 8. Patients with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months. 9. Presence of active infection or systemic use of antibiotics within 72 hours of treatment. 10. Significant co-morbid condition or disease, which in the judgment of the Investigator, would place the patient at undue risk or interfere with the study. Examples include, but are not limited to sepsis and recent significant traumatic injury. 11. Known human immunodeficiency virus (HIV) positivity. 12. Known hypersensitivity to IPI-926, or any of the excipients in IPI-926 or placebo capsules. 13. Pregnant or lactating women. 14. Concurrent administration of the medications or foods which are known to be moderate or strong inhibitors of CYP3A4 activity (see Appendix 1).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Compare progression-free survival (PFS) in patients with metastatic or locally advanced (unresectable) chondrosarcoma administered IPI-926 or placebo. • Evaluate the safety of IPI-926 in patients with metastatic or locally advanced(unresectable) chondrosarcoma ;Secondary Objective: • Compare time to progression (TTP), overall survival (OS), overall response rate (ORR), and response duration in patients with metastatic or locally advanced (unresectable) chondrosarcoma administered IPI-926 or placebo. • Assess PFS, TTP, OS, and ORR following administration of IPI-926 in the open label portion of the study. • Examine the pharmacokinetics of IPI 926 and its metabolite IPI-541 ;Primary end point(s): • PFS, defined as time from randomizationto disease progression or death, following administration of IPI-926 or placebo in patients with metastatic or locally advanced (unresectable) chondrosarcoma. • Incidence of reported adverse events and abnormal laboratory test results. ;Timepoint(s) of evaluation of this end point: Tumor imaging is conducted every 4 weeks for 8 weeks, then every 8 weeks for 12 weeks, then every 12 weeks until tumor progression. Survival is evaluated continuously throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • TTP, defined as time from randomization to disease progression, in patients with metastatic or locally advanced (unresectable) chondrosarcoma administered IPI-926 or placebo. • OS, defined as time from randomization to death, in patients with metastatic or locally advanced (unresectable) chondrosarcoma administered IPI-926 or placebo. • ORR, defined as an overall response of either partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, in patients with metastatic or locally advanced (unresectable) chondrosarcoma administered IPI 926 or placebo. • PFS, TTP, OS, and ORR following administration of IPI-926 in the open label portion of the study. • Plasma concentrations of IPI 926 and its metabolite IPI 541. ;Timepoint(s) of evaluation of this end point: Tumor imaging related 2ry endpoints (time to progression (TTP), overall response rate (ORR), and response duration) will be evaluated every 4 weeks for 8 weeks, then every 8 weeks for 12 weeks, then every 12 weeks until tumor progression. Overall survival is evaluated continuously (after study discontinuation then approximately every 3 months for up to 2 years followed by contact at 3 years to collect survival data). Pharmacokinetics are evaluated pre-dose on Day 1 of Cycles 1, 2, and 3, and on Day 1 of every third cycle thereafter. | — |
Countries
Australia, Austria, Canada, Germany, Italy, Netherlands, Norway, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactIPI-926-04 Trial Information
Infinity Pharmaceuticals, Inc
Outcome results
None listed