E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Colorectal Carcinoma of the Liver |
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E.1.1.1 | Medical condition in easily understood language |
colorectal cancer with metastases in the liver |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Objective of this study is to evaluate the efficacy and safety of TheraSphere in patients with metastatic colorectal cancer of the liver who have progressed with first line chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria:
1. Must be a male or female, 18 years of age or older, and of any ethnic or racial group
2. If primary tumor has not been resected, it must be clinically stable
3. Must have colorectal cancer with unresectable metastatic disease to the liver (unresectable unilobar or bilobar disease) who have disease progression in the liver with oxaliplatin or irinotecan based first line chemotherapy
4. Must be eligible to receive second-line standard-of-care chemotherapy with either
1) an oxaliplatin-based chemotherapy regimen, or
2) an irinotecan-based chemotherapy regimen
5. Must have baseline efficacy images with measurable target tumors in the liver according to RECIST 1.1 using standard imaging techniques taken within 28 days prior to randomization. Images must be taken after, or at the time of completion of first line chemotherapy
6. Tumor replacement <50% of total liver volume
7. Current ECOG Performance Status score of 0-1 through screening to first treatment on study.
8. Will have completed the first line chemotherapy regimen at least 14 days prior to the initiation of 2nd line chemotherapy under the protocol
9. Patient is willing to participate in the study and has signed the study informed consent.
10. Serum creatinine <2.0 mg/dL
11. Serum bilirubin up to 1.2 x upper limit of normal
12. Albumin >3.0 g/dL
13. Must not have a history of hepatic encephalopathy
14. Must not have any contraindications to angiography and selective visceral catheterization such as bleeding diathesis or coagulopathy that is not correctable by usual therapy of hemostatic agents (e.g. closure device)
15. No history of severe peripheral allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically
16. Must have neutrophil count >1200/mm3 (1.2x109/L)
17. No presentation of pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease
18. No cirrhosis or portal hypertension
19. Must not have received prior external beam radiation treatment to the liver
20. Must not have received any prior intra-arterial liver directed therapy, including TACE, or Y-90 microsphere therapy
21. Must not have any planned liver directed therapy or radiation therapy
22. Must not have planned treatment with biological agents within 28 days prior to receiving TheraSphere
23. Must not have undergone any intervention for, or compromise of, the Ampulla of Vater
24. Must not have any clinically evident ascites (trace ascites on imaging is acceptable)
25. Must not have any toxicities due to prior cancer therapy that have not resolved before the initiation of study treatment, if the Investigator determines that the continuing complication will compromise the safe treatment of the patient
26. Must not have any significant life-threatening extra-hepatic disease, including patients who are on dialysis, have unresolved diarrhea, have serious unresolved infections including patients who are known to be HIV positive or have acute HBV or HCV
27. Must not have any confirmed extra-hepatic metastases. Limited indeterminate extra-hepatic lesions in the lung and/or lymph nodes are permitted (up to 5 lesions in the lung, with each individual lesion <1 cm; any number of lymph nodes with each individual node <1.5 cm)
28. Must not have any contraindications to the planned second line standard-of-care chemotherapy regimen
29. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization, and must not be breastfeeding and must agree to use contraceptive for duration of study
30. Must not have participated in a clinical trial with an investigational therapy within 30 days prior to randomization
31. Must not have any co-morbid disease or condition that would place the patient at undue risk and preclude the safe use of TheraSphere Treatment, in the investigator’s judgment |
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E.4 | Principal exclusion criteria |
No exclusion criteria listed |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS) according to RECIST Criteria v.1.1 from time of randomization.
Hepatic Progression-Free Survival (HPFS), defined as the time from randomization to the date of disease progression in the liver according to RECIST 1.1, or death. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 8 weeks following randomization |
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E.5.2 | Secondary end point(s) |
• Overall Survival (OS) Time, calculated from randomization to death.
- Time to symptomatic progression (TTSP)
- Disease Control Rate (DCR)
- Objective Response Rate (ORR)
- Quality of Life Assessment
- Adverse events and reportable serious adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Overall survival: Day 0 to death
- HPFS, TTSP, Disease control Quality of Life assessment, adverse events: Day 0, every 8 weeks until the date of disease progression, or death.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hong Kong |
Italy |
Korea, Republic of |
Singapore |
Spain |
Switzerland |
Taiwan |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 11 |