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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03299660
Ethics application status
Date submitted
24/09/2017
Date registered
3/10/2017

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
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
Timepoint [1] 0 0
At 8 weeks post LCCRT
Secondary outcome [2] 0 0
Overall FDG PET response
Timepoint [2] 0 0
At 8 weeks post LCCRT
Secondary outcome [3] 0 0
Define toxicity during administration of PDL1 inhibitor and post-surgery
Timepoint [3] 0 0
From consent until 4 weeks post surgery
Secondary outcome [4] 0 0
Determine rate of downstaging
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
Sex
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
NA
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/02/2023
Sample size
Target
Accrual to date
Final
37
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Royal North Shore - St Leonards
Recruitment hospital [3] 0 0
Box Hill Hospital - Box hill
Recruitment hospital [4] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [6] 0 0
Monash Health - Melbourne
Recruitment hospital [7] 0 0
Alfred Hospital - Prahran
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
3128 - Box hill
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
3002 - Melbourne
Recruitment postcode(s) [6] 0 0
- Melbourne
Recruitment postcode(s) [7] 0 0
3000 - Prahran

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03299660