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Rectal CancerPhase 2NCT03299660

Avelumab With Chemoradiation in Locally Advanced Rectal Cancer

A Phase 2 study testing Avelumab, 5 Fluorouracil and Capecitabine Pill in people with Rectal Cancer, run by Peter MacCallum Cancer Centre, Australia at 7 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rectal Cancer
What is being tested?
Avelumab, 5 Fluorouracil and Capecitabine Pill
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
7 sitesAustralia
Study dates
30 Apr 2018to 28 Feb 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female aged ≥ 18 years at screening
  • Patients with histologically confirmed rectal adenocarcinoma clinical stage T3bN1-N2M0, T3c/dN0-N2M0, T4N0-N2M0 (see Appendix 1),1 as defined by pelvic MRI
  • 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
  • Lower border of tumour must be within 12 cm from anal verge
  • Measurable disease by RECIST1.12
  • ECOG Performance Status 0-1
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  • Patients must be willing to provide fresh (where possible) and archival tumour tissue samples for translational studies at specified time points
  • Adequate organ function
  • Absolute neutrophil count ≥1.5 x 109/L
  • Platelet count ≥100 x 109/L
  • Haemoglobin ≥ 90 g/L (may have been transfused)
  • Creatinine ≤ 1.5 x upper normal limit OR measured creatinine clearance ≥ 50 mL/minute
  • Total bilirubin ≤ 1.5 x upper normal limit
  • AST/ALT ≤ 2.5 x upper normal limit
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test at screening
  • 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
  • Has provided written informed consent for the trial
  • Agrees to comply with trial therapy or trial-related investigations and evaluations

Who cannot join

  • Patients with disease outside the pelvis
  • Prior pelvic radiotherapy
  • Participation in another interventional clinical trial within 30 days of registration (participation in observational studies are permitted)
  • Concurrent anti-cancer treatment
  • Concurrent treatment with a non-permitted drug (Section 8.3.2)
  • Major surgery for any reason within 4 weeks of registration (except defunctioning stoma creation with the patient having fully recovered from this procedure)
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  • 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
  • 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
  • Active or history of immunodeficiencies
  • Has received prior therapy with an anti-PD1, anti-PDL1, anti-PDL2 or anti-CTLA-4 agents
  • 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.
  • Has an active infection requiring systemic therapy
  • 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
  • Prior malignancies within 3 years of registration (with the exception of non- melanomatous skin cancer)
  • Prior organ transplantation, including allogeneic stem-cell transplantation
  • A known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS)
  • 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)
  • 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)
  • Is pregnant or lactating
  • Vaccination within 4 weeks of registration and while on trials is prohibited except for administration of inactivated vaccines
  • Known deficiency of dihydropyrimidine dehydrogenase

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Australia7 sites

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Cabrini Hospital

    Malvern, Victoria, 3144

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3002

  • Monash Health

    Melbourne, Victoria

  • Alfred Hospital

    Prahran, Victoria, 3000

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Royal North Shore

    St Leonards, New South Wales, 2065

Other trials in Australia

About this study

Official title: Phase II Trial PD-L1/PD-1 Blockade Avelumab (MSB0010718C) With Chemoradiotherapy for Locally Advanced Resectable Rectal Cancer

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.

Conditions
Rectal Cancer
Being tested
Avelumab, 5 Fluorouracil, Capecitabine Pill, Radiotherapy, Surgical Resection
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called MSB0010718C

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

  • 5 FluorouracilDrug

    5FU continuous infusion 225mg/m2/day during radiotherapy

  • Capecitabine PillDrug

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

  • RadiotherapyRadiation

    50.4 Gy in 28 fractions delivered over 5.5 weeks as 5 fractions/week

  • Surgical ResectionProcedure or surgery

    Surgical resection of tumour mass post radiotherapy and chemotherapy

Study groups in NCT03299660
Study groupRoleWhat they receive
AvelumabExperimentalLong 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
Receives: Drug: Avelumab; Drug: 5 Fluorouracil; Drug: Capecitabine Pill; Radiation: Radiotherapy; Procedure: Surgical Resection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: At time of resection i.e.16 -18 weeks post commencement of treatment

Secondary outcomes (4)

  1. Response as per structural imaging

    Describe radiological response rate based on Pelvic MRI post PD-L1 blockade as per RECIST 1.1

    Measured: At 8 weeks post LCCRT

  2. Overall FDG PET response

    Describe FDG-PET response rate post PDL1 blockade as per PERCIST

    Measured: At 8 weeks post LCCRT

  3. Define toxicity during administration of PDL1 inhibitor and post-surgery

    Worst grade AE's and SAE's CTCAE version 4.03

    Measured: From consent until 4 weeks post surgery

  4. 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.

    Measured: At time of surgical resection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2017
  2. Study start30 Apr 2018
  3. Primary completion28 Feb 2023
  4. Study completion28 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
All participants will receive standard LCCRT treatment followed by 4 cycles of Avelumab followed by surgical resection
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03299660
Sponsor's protocol ID
AveRec
Status last verified
Mar 2023
First submitted
24 Sep 2017
Last updated
16 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab, 5 Fluorouracil and Capecitabine Pill in people with Rectal Cancer, run by Peter MacCallum Cancer Centre, Australia at 7 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Response rate (time frame: At time of resection i.e.16 -18 weeks post commencement of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03299660.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2023.

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