E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or Locally Advanced Chondrosarcoma |
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E.1.1.1 | Medical condition in easily understood language |
Chondrosarcoma is a type of cancer that arises in the cartilage (the tissue that covers the ends of bones in joints). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008734 |
E.1.2 | Term | Chondrosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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
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E.2.2 | Secondary objectives of the trial |
• 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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.
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E.4 | Principal 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 <8.0 g/dL (80 g/L) (may be increased to this level with transfusion as long as there is no evidence of active bleeding).
6. Inadequate hepatic function defined by:
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >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). |
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | 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. |
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E.5.2 | 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.
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |