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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03299660




Registration number
NCT03299660
Ethics application status
Date submitted
24/09/2017
Date registered
3/10/2017
Date last updated
14/05/2020

Titles & IDs
Public title
Avelumab With Chemoradiation in Locally Advanced Rectal Cancer
Scientific title
Phase II Trial PD-L1/PD-1 Blockade Avelumab (MSB0010718C) With Chemoradiotherapy for Locally Advanced Resectable Rectal Cancer
Secondary ID [1] 0 0
AveRec
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab
Treatment: Drugs - 5 Fluorouracil
Treatment: Drugs - Capecitabine Pill
Treatment: Other - Radiotherapy
Treatment: Surgery - Surgical Resection

Experimental: Avelumab - Long course chemoradiotherapy (LCCRT) comprised of 50.4 Gy radiotherapy in conjunction with 5FU (225mg/m2/day continuous infusion)/Capecitabine (825 mg/m2 BID on RT days) over 5. 5 weeks, followed by 4 cycles of Avelumab. This is then followed up with surgical resection


Treatment: Drugs: Avelumab
Avelumab 10 mg/Kg every 2 weeks for 4 cycles post LCCRT

Treatment: Drugs: 5 Fluorouracil
5FU continuous infusion 225mg/m2/day during radiotherapy

Treatment: Drugs: Capecitabine Pill
Can be administered in place of 5FU infusion. Dose = 825 mg/m2 twice a day on each day of radiotherapy

Treatment: Other: Radiotherapy
50.4 Gy in 28 fractions delivered over 5.5 weeks as 5 fractions/week

Treatment: Surgery: Surgical Resection
Surgical resection of tumour mass post radiotherapy and chemotherapy

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathological Response rate - To investigate the role of PD-L1 blockade for rectal cancer following neoadjuvant LCCRT, prior to definitive surgical resection, in terms pathological response rates. Assessed by tumour regression grade in resected rectal cancers post LCCRT at the time of definitive surgery: according to Ryan et al
Timepoint [1] 0 0
At time of resection i.e.16 -18 weeks post commencement of treatment
Secondary outcome [1] 0 0
Response as per structural imaging - Describe radiological response rate based on Pelvic MRI post PD-L1 blockade as per RECIST 1.1
Timepoint [1] 0 0
At 8 weeks post LCCRT
Secondary outcome [2] 0 0
Overall FDG PET response - Describe FDG-PET response rate post PDL1 blockade as per PERCIST
Timepoint [2] 0 0
At 8 weeks post LCCRT
Secondary outcome [3] 0 0
Define toxicity during administration of PDL1 inhibitor and post-surgery - Worst grade AE's and SAE's CTCAE version 4.03
Timepoint [3] 0 0
From consent until 4 weeks post surgery
Secondary outcome [4] 0 0
Determine rate of downstaging - Patients will be considered downstaged if the pathologic T or N stage at surgery assessment is lower than the initial radiological stage.
Timepoint [4] 0 0
At time of surgical resection

Eligibility
Key inclusion criteria
1. Male or female aged = 18 years at screening

2. Patients with histologically confirmed rectal adenocarcinoma clinical stage
T3bN1-N2M0, T3c/dN0-N2M0, T4N0-N2M0 (see Appendix 1),1 as defined by pelvic MRI

3. Planned to receive neoadjuvant long course chemoradiotherapy (50.4 Gy, with infusional
5FU or capecitabine) followed by curative total mesorectal excision plus
abdomino-perineal resection or anterior resection

4. Lower border of tumour must be within 12 cm from anal verge

5. Measurable disease by RECIST1.12

6. ECOG Performance Status 0-1

7. Patients must be willing to provide fresh (where possible) and archival tumour tissue
samples for translational studies at specified time points

8. Adequate organ function

1. Absolute neutrophil count =1.5 x 109/L

2. Platelet count =100 x 109/L

3. Haemoglobin = 90 g/L (may have been transfused)

4. Creatinine = 1.5 x upper normal limit OR measured creatinine clearance = 50
mL/minute

5. Total bilirubin = 1.5 x upper normal limit

6. AST/ALT = 2.5 x upper normal limit

9. Female patients of childbearing potential must have a negative urine or serum
pregnancy test at screening

10. Both male and female patients should be willing to use highly effective contraception
(that is, methods with a failure rate of less than 1% per year) if the risk of
conception exists

11. Has provided written informed consent for the trial

12. Agrees to comply with trial therapy or trial-related investigations and evaluations
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with disease outside the pelvis

2. Prior pelvic radiotherapy

3. Participation in another interventional clinical trial within 30 days of registration
(participation in observational studies are permitted)

4. Concurrent anti-cancer treatment

5. Concurrent treatment with a non-permitted drug (Section 8.3.2)

6. Major surgery for any reason within 4 weeks of registration (except defunctioning
stoma creation with the patient having fully recovered from this procedure)

7. Current use of immunosuppressive medication. Except for the following: (a) intranasal,
inhaled, topical steroids, or local steroid injection (e.g., intra-articular
injection); (b). Systemic corticosteroids at physiologic doses = 10 mg/day of
prednisone or equivalent; (c). Steroids as premedication for hypersensitivity
reactions (e.g., CT scan premedication); (d) Short-term administration of systemic
steroids (that is, for allergic reactions or the management of irAEs) is allowed while
on study.

Note: Patients receiving bisphosphonate or denosumab are eligible

8. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
diseases not requiring immunosuppressive treatment are eligible

9. Active or history of immunodeficiencies

10. Has received prior therapy with an anti-PD1, anti-PDL1, anti-PDL2 or anti-CTLA-4
agents

11. Has clinically significant (that is, active) cardiovascular disease: cerebral vascular
accident / stroke (< 6 months prior to registration), myocardial infarction (< 6
months prior to registration), unstable angina, congestive heart failure (New York
Heart Association Classification Class = II), or serious cardiac arrhythmia requiring
medication.

12. Has an active infection requiring systemic therapy

13. Other severe acute or chronic medical conditions including immune colitis,
inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
conditions including recent (within the past year) or active suicidal ideation or
behaviour; or laboratory abnormalities that may increase the risk associated with
study participation or study treatment administration or may interfere with the
interpretation of study results and, in the judgment of the investigator, would make
the patient inappropriate for entry into this study

14. Prior malignancies within 3 years of registration (with the exception of non-
melanomatous skin cancer)

15. Prior organ transplantation, including allogeneic stem-cell transplantation

16. A known history of testing positive for HIV or known acquired immunodeficiency
syndrome (AIDS)

17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive
HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive)

18. Known prior severe hypersensitivity to investigational product or any component in its
formulations, including known severe hypersensitivity reactions to monoclonal
antibodies (CTCAE v4.03 grade = 3)

19. Is pregnant or lactating

20. Vaccination within 4 weeks of registration and while on trials is prohibited except
for administration of inactivated vaccines

21. Known deficiency of dihydropyrimidine dehydrogenase

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This trial is investigating the inclusion of avelumab post long-course chemo-radiotherapy in
patients with resectable locally advanced rectal cancer. It is hypothesised that this may
enhance the pathological and imaging response rates whilst potentially reducing the relapse
rates. Participants will receive standard long course chemoradiotherapy (LCCRT) treatment
with radiotherapy and 5-fluorouracil (5 FU)/Capecitabine for 6 weeks, this then followed by 4
cycles of Avelumab and then surgical resection. The trial will measure disease response just
prior to surgery and participants will be followed up for a minimum of 18 months (from study
entry) and up to 42 months.
Trial website
https://clinicaltrials.gov/show/NCT03299660
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Michael, A/Prof
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michael Michael, A/Prof
Address 0 0
Country 0 0
Phone 0 0
+61385597860
Fax 0 0
Email 0 0
Michael.Michael@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03299660