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eoadjuvant treatment in rectal cancer with radiotherapy followed by atezolizumab and bevacizumab (TARZAN-trial)

Phase 2
Recruiting
Conditions
rectal cancer
rectum
10017991
Registration Number
NL-OMON52486
Lead Sponsor
ederlands Kanker Instituut
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
Not specified
Target Recruitment
38
Inclusion Criteria

- Signed informed consent form
- Age >=18 years
- 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 rectal cancer (cT1-3bN0 MRF-) in patients who wish to pursue organ
preservation
- No signs of distant metastases on CT of thorax and abdomen, MRI pelvis < 4
weeks to inclusion
- 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
- Evaluable disease
- Adequate hematologic and end-organ function

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 , or
treated with expected curative outcome
- 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
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
recurrent drainage procedures
- Uncontrolled tumor pain
- 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
- Current or recent (within 10 days of study enrollment) use of
acetylsalicylic acid (> 325 mg/day), clopidogrel (> 75 mg/day) or current or
recent (within 10 days of C1D1) use of therapeutic oral or parenteral
anticoagulants or thrombolytic agents for therapeutic purposes

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Clinical complete and near-complete response rate (cCCR) assessed at week 12<br /><br>post-RT:<br /><br>• Complete response is defined as lack of any visible lesion at rectoscopy*<br /><br>(except a flat scar, telangiectasia or whitening of the mucosa; and lack of<br /><br>absence of any residual tumor in the primary site and draining lymph nodes on<br /><br>imaging with MRI including DWI<br /><br>• Near complete response is defined as only a small flat ulceration on<br /><br>endoscopy and/or a small residual focus on DWI, with otherwise no signs of<br /><br>residual tumor.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>• Safety: incidence and severity of AEs (with severity determined according to<br /><br>NCI CTCAE v4.03), vital signs and clinical laboratory test results.<br /><br>• Pre-operative treatment-related complications leading to delays in systemic<br /><br>treatment and/or surgery (excluding non-treatment-related and logistical<br /><br>reasons).<br /><br>• Relapse-free survival (RFS), defined as the time from study enrolment to<br /><br>disease recurrence or disease-related death during follow-up<br /><br>• Local recurrence rate (LRR) at 1 year follow-up<br /><br>• Proportion of patients who undergo organ preserving treatment<br /><br>• Pathological complete and near-complete response (pCR), defined as Mandard<br /><br>TRG 1-2, if available<br /><br>• Radiological tumor regression using MRI (ESGAR consensus guidelines) </p><br>
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