E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
adenocarcinoma of the rectum |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10038038 |
E.1.2 | Term | Rectal 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 |
To explore efficacy of neoadjuvant atezolizumab and bevacizumab following radiotherapy in low- to intermediate-risk rectal cancer |
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E.2.2 | Secondary objectives of the trial |
• To evaluate safety/tolerability and pre-operative treatment-related complications with atezolizumab and bevacizumab following radiotherapy • To explore efficacy with regard to preventing/delaying disease relapse and to organ preservation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent form - Age ≥18 years - Able to comply with the study protocol, in the investigator’s judgment - Histologically confirmed adenocarcinoma of the rectum, and known microsatellite stability status - Patients with intermediate risk rectal cancer (cT1-3N1 or cT3c/dN0 MRF-) or low risk distal rectal cancer (cT1-3bN0 MRF-) in patients who wish to pursue organ preservation - No signs of distant metastases - patients must be willing to undergo proctoscopy and biopsies prior to start of treatment and during treatment at defined timepoints - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Life expectancy > 6 months - Evaluable disease - Adequate hematologic and end-organ function
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E.4 | Principal exclusion criteria |
- Clinical symptoms or radiological suspicion of perforation - Other malignancies within 3 years prior to registration in the study with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year overall survival > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent). - Prior radiation therapy within 30 days prior to C1D1 and/or persistence of radiation-related adverse effects or previous radiation therapy preventing 5x5Gy as specified in this study - Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past - Spinal cord compression not definitively treated with surgery and/or radiation - Treatment with any investigational agent or approved therapy within 28 days or two investigational agent half-lives (whichever is longer) prior to C1D1 - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-PD-1 and anti-PD-L1, with MEK inhibitor or VEGF/VEGFR inhibitors - History of clinically significant cardiac or pulmonary dysfunction - Autoimmune conditions - Infectious diseases |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical complete and near-complete response rate (cCCR) assessed at week 12 post-RT: - Complete response is defined as lack of any visible lesion at rectoscopy* (except a flat scar, telangiectasia or whitening of the mucosa; and lack of absence of any residual tumor in the primary site and draining lymph nodes on imaging with MRI including DWI - Near complete response is defined as only a small flat ulceration on endoscopy and/or a small residual focus on DWI, with otherwise no signs of residual tumor.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks post radiotherapy |
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E.5.2 | Secondary end point(s) |
- Safety: incidence and severity of AEs (with severity determined according to NCI CTCAE v4.03), vital signs and clinical laboratory test results. - Pre-operative treatment-related complications leading to delays in systemic treatment and/or surgery (excluding non-treatment-related and logistical reasons). - Relapse-free survival (RFS), defined as the time from study enrolment to disease recurrence or disease-related death during follow-up - Local recurrence rate (LRR) at 1 year follow-up - Proportion of patients who undergo organ preserving treatment - Pathological complete and near-complete response (pCR), defined as Mandard TRG 1-2, if available - Radiological tumor regression using MRI (ESGAR consensus guidelines)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
measured within 1 year after inclusion |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |