This study has been transitioned to CTIS with ID 2024-517119-59-00 check the CTIS register for the current data. *- To explore efficacy of neoadjuvant atezolizumab and bevacizumab following radiotherapy in low- to intermediate-risk rectal cancer• To…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
• 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)
Background summary
In a substantial proportion of patients with rectal cancer, neoadjuvant
(chemo-)radiotherapy can result in a complete response, obviating the need for
major surgery and often avoiding a definitive stoma. Although still
controversial, this so-called organ preservation approach can markedly improve
the patients* quality of life. In this context, exploring the therapeutic
potential of combined inhibition of PD-L1 and VEGF to increase the rate and
depth of responses following standard-of-care radiotherapy in low and
intermediate risk rectal cancers is a compelling path forward in organ
preservation.
Overall, combining radiotherapy with immune stimulation may support the immune
modulating potential of RT by interfering with the local immunosuppressive
milieu.
The immunomodulatory effect of bevacizumab is expected to increase CD8+ T cell
recruitment and relieve intratumoral immunosuppression, thereby boosting the
effects of atezolizumab.
Study objective
This study has been transitioned to CTIS with ID 2024-517119-59-00 check the CTIS register for the current data.
*- To explore efficacy of neoadjuvant atezolizumab and bevacizumab following
radiotherapy in low- to intermediate-risk rectal cancer
• 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
Study design
In this single-center, open-label exploratory study evaluating the safety and
efficacy of atezolizumab and bevacizumab following standard-of-care RT in stage
1-3 rectal cancer, a minimum of 38 patients with rectal cancers will be
enrolled.
• 5 x 5Gy radiotherapy (RT) followed 3 weeks later by
• 3 x bevacizumab 5mg/kg IV at 2-weekly (q2w) intervals
- 3 x atezolizumab 840mg IV q2w, starting 2 weeks after the first
bevacizumab dose
Intervention
• 5 x 5Gy radiotherapy (RT) followed 3 weeks later by
• 3 x bevacizumab 5mg/kg IV at 2-weekly (q2w) intervals
• 3 x atezolizumab 840mg IV q2w, starting 2 weeks after the first bevacizumab
dose
Study burden and risks
Patients will undergo a proctoscopy for determination of the required resection
margins and for acquisition of study-related biopsies. Repeat scopy for this
patient category is common practice at our institute prior to start of
treatment. At baseline and before each treatment, blood samples will be drawn,
for both follow-up of treatment effects and for research purposes.
Participation will mean 2 additional scopies, one after radiotherapy and before
start monotherapy and 1 prior to the first cycle of combination treatment.
Site visits for the treatment with chemotherapy and immunotherapy is comparable
to that of patients not being treated within the study.
Additional risks of the investigational treatment includes immune related side
effects associated with atezolizumab
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-517119-59-00 |
| EudraCT | EUCTR2018-002463-25-NL |
| CCMO | NL66124.031.18 |