Bone Cancer of the Cartilage Metastatic or Locally Advanced (Unresectable) Chondrosarcoma
Conditions
Interventions
This is a double-blind, placebo-controlled study. Patients will be randomly
assigned in a 2:1 ratio to receive IPI-926 or placebo.
This study also includes an optional open-label portion for patients
Sponsors
Infinity Pharmaceuticals, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients are eligible for inclusion in the study if they meet the following 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 55 years 12 consecutive months) must have a negative serum or urine β human chorionic gonadotropin (βhCG) 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.
Exclusion criteria
Exclusion criteria: Patients are to be excluded from the study if they meet any of the following criteria: 1. Other invasive malignancies diagnosed 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. Current 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 |
|---|---|
| The primary endpoints are: • PFS, defined as time from randomization to 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints are: • 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. The exploratory endpoints are: • Changes in BPI-SF scores in patients treated with IPI-926 or placebo. • Evidence of Hedgehog signaling inhibition in tumor tissue. • Evaluation of tumor markers, tumor-stroma interaction markers, including the presence of primary cilia, and markers reflecting the activity of the Hh signaling pathway using analysis of protein, DNA, and RNA. • Evaluation for the presence of additional tumor specific protein, DNA or RNA biomarkers to study the association between molecular characteristics of the tumor with response or clinical benefit to IPI-926. • Changes in calcification within the tumor and surrounding stroma using CT scan or MRI. | — |
Countries
Netherlands
Outcome results
None listed