E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Colorectal cancer (Stage II [high risk] and Stage III) |
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E.1.1.1 | Medical condition in easily understood language |
Patient with a high risk form of cancer affecting the colon and rectum. |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010034 |
E.1.2 | Term | Colorectal cancer stage III |
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 | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010033 |
E.1.2 | Term | Colorectal cancer stage II |
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 |
To demonstrate superiority of RO7198457 compared to “watchful waiting” in terms of Disease Free Survival (DFS) (i.e., prolonged DFS time) in chemotherapy pretreated patients. |
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E.2.2 | Secondary objectives of the trial |
-To assess the efficacy of RO7198457 compared to “watchful waiting” in terms of relapse-free survival (RFS), time to recurrence (TTR) time to treatment failure (TTF), and overall survival (OS). -To assess anti-tumor efficacy. -To assess the safety and tolerability of RO7198457.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must be a man or woman of at least 18 years of age. 2. Patients must have given informed consent indicating that they understand the purpose of and procedures required for the trial and are willing to participate in the trial. 3. Patients must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III colon cancer per AJCC 2017 that has been surgically totally resected (R0 confirmed by pathology report). 4. Patients must have detectable ctDNA prior to start of AdCTx (except for the Biomarker Cohort), detected with the Avenio Oncology Assay (AOA) Surveillance Test. 5. Patients must have an ECOG Performance Status of 0-1. 6. Patients must have organ and bone marrow function, in line with the criteria further detailed in the protocol.
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E.4 | Principal exclusion criteria |
1. Patients with uncontrolled intercurrent illness, including any of but not limited to the criteria outlined in the protocol. 2. Diagnosed Microsatellite instability (MSI) high tumors. 3. Prior therapy with any of the medications further detailed in the protocol. 4. Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy. 5. Patients who are breastfeeding at screening visits 2 or 3, or who plan to breastfeed during the trial, starting after the start of treatment with RO7198457 and continuously until at least 90 d after receiving the last dose of RO7198457, further detailed in the protocol 6. Patients who have had prior splenectomy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Disease free survival (DFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From the time from randomization to occurrence of any of the following events, whichever occurs first:
-Locoregional recurrence or distant metastases as determined by an independent central radiology assessment. -Occurrence of second primary (same or other) cancer as determined by an independent central radiology assessment. -Death from any cause. -Loss to follow-up is censored. |
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E.5.2 | Secondary end point(s) |
-Relapse Free Survival (RFS) -Time to recurrence (TTR) -Time to treatment failure (TTF) -Overall survival (OS) -Change of Circulating tumor DNA (ctDNA) status -Occurrence of treatment emergent adverse events (TEAEs), including Grade 3+, serious, fatal TEAEs by relationship. -Occurrence of dose reduction and discontinuation of R07198457 due to a TEAE
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomization to occurrence of any of the following events, whichever occurs first:
Locoregional recurrence or distant metastases as determined by the investigator Death from any cause (RFS, OS) Death from same cancer (TTR) Death from any cause except non-cancer related death (TTF) Occurrence of second primary (same or other) cancer as determined by the investigator is ignored (RFS, TTR) Occurrence of second primary (same or other) cancer as determined by the investigator (TTF) Loss to follow-up is censored (RFS) Loss to follow-up and deaths from other cancer, non-cancer-related deaths, treatment-related deaths are censored (TTR) Loss to follow-up and non–cancer-related deaths are censored (TTF)
ctDNA status: every 3 months.
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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 | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
"Watchful waiting" control arm |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 24 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
United States |
Belgium |
Germany |
Spain |
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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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The end of the trial will be declared at the time at which:
-All patients have discontinued RO7198457 treatment; and -All patients have completed safety follow-up assessment at day 90 subsequent to last dose; and -The primary analyses are mature to be performed (i.e., at least 124 events have occurred); and -All patients have been followed-up for at least 48 months subsequent to first dose/randomization, are lost to follow-up or have died. or -The sponsor discontinues 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 | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |