The UNSCARRed Study: UNresctable Squamous Cell Carcinoma Treated With Avelumab and Radical Radiotherapy (UNSCARRed)
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|ClinicalTrials.gov Identifier: NCT03737721|
Recruitment Status : Recruiting
First Posted : November 9, 2018
Last Update Posted : July 7, 2020
The purpose of this study is to find out what effects the combination of radiation therapy and Avelumab have on you and your cancer. The effectiveness of this treatment as well as what side effects occur will both be studied.
Squamous cell carcinoma of the skin is the most commonly diagnosed cancer. Risk factors for the development of squamous cell cancer include ultraviolet (sun) exposure, as well as increasing age. In the majority of instances, a minor surgical procedure is curative. Less commonly, squamous cell carcinoma cannot be removed surgically, due to the location and/or extent of the cancer, or due to patient-specific factors which would make surgery unsafe (for instance, the presence of unrelated medical illnesses such as heart disease or stroke).
When squamous cell carcinoma cannot be removed surgically, radiation therapy may serve as an effective alternative treatment. Squamous cell carcinomas are typically very sensitive to radiation, and in some instances radiation therapy may also cure a person of their cancer.
While some people may be cured by radiation therapy, not all people are. This study is investigating the combination of radiation therapy and immune therapy. When given together, more patients may be cured of their cancer.
Immune therapy is effective for the treatment of squamous cell carcinoma. In clinical trials, more than half of patients benefit from immune therapy. Immune therapy is not chemotherapy. Instead, immune therapy involves the infusion of antibodies which target a person's own immune system. Immune therapy "re-activates" a person's own immune system against their cancer.
The treatment offered within this clinical trial includes daily radiation treatments as well as immunotherapy treatments administered once every two weeks. The immunotherapy in use is a drug called Avelumab, which is an antibody that helps your body's immune system fight cancer.
Health Canada, the regulatory body that oversees the use of natural health products, drugs and devices in Canada, has not approved the sale or use of this product to treat this kind of cancer, although they have allowed its use in this study
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma of the Skin||Combination Product: Avelumab and Radical radiotherapy||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This study has been designed as an open-label, non-randomized, single-arm phase II study to investigate the feasibility and efficacy of Avelumab in combination with radiation therapy in patients with unresectable cuSCC.|
|Masking:||None (Open Label)|
|Official Title:||UNresectable Squamous Cell Carcinoma Treated With Avelumab and Radical Radiotherapy. A Study to Evaluate the Efficacy and Safety of the Combined Use of Avelumab With Radiation Therapy for the Treatment of Unresectable Cutaneous Squamous Cell Carcinoma|
|Actual Study Start Date :||April 12, 2019|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2023|
Experimental: Avelumab and Radical radiotherapy
Single-arm combining Avelumab with radical radiotherapy.
Combination Product: Avelumab and Radical radiotherapy
A single-arm, interventional study combining Avelumab with radical radiotherapy. Avelumab will be delivered on a 14-day cycle, with the first cycle administered 14 days in advance of the radiation therapy start date; 63-66 Gy radiation will be delivered over 30 daily fractions concurrent with an additional 4 cycles of Avelumab
- Objective response rate (assessing change in tumour response before treatment vs after) [ Time Frame: Primary analysis to occur approximately 36 weeks after LPFV. Baseline staging at screening,repeated at 90 day fup and confirmatory scan ]Associated with combination Avelumab/radiation therapy (defined as the proportion of patients achieving either a partial response or a complete response as best-overall response per RECIST criteria 1.1)
- Progression-free survival [ Time Frame: PFS will be based on the disease assessment or date of death provided by the investigator. The analysis of PFS will be scheduled to occur approximately 90 days following completion of the 24 month follow-up period for the final patient enrolled to study ]PFS is defined as the time between the date of treatment initiation and the date of disease progression (determined utilizing RECIST 1.1 criteria) or death (whatever the cause), whichever occurs first. For patients who remain alive and whose disease has not progressed, PFS data will be censored on the date of the last tumour assessment on study for patients who do not have objective tumour progression and who do not die while on study
- Clinical and pathological response rate [ Time Frame: The analysis of clinical and pathological response will be conducted within 90 days of enrollment of the last patient to study ]associated with Avelumab monotherapy (clinical response rate per RECIST 1.1; pathological response rate defined as the proportion of patients who, upon post-Avelumab monotherapy re-biopsy, demonstrate ≥ 10% increase tumor necrosis versus pre-treatment biopsy)
- Safety analysis: CTCAE v.4.03 [ Time Frame: Delegated study personnel will assess the patients for adverse events at baseline through to study completion per protocol (Baseline, cycles 1-5 (each cycle is 14 days), and in follow up at 30 days, 90 days and every 12 weeks up to 2 years). ](treatment-related and non-related adverse events per CTCAE v.4.03)
- Utility of tumoral PD-L1 expression as a predictive and prognostic biomarker [ Time Frame: Tumor biopsies will be obtained prior to treatment (baseline), following Avelumab monotherapy (post-cycle 1 treatment) and following completion of Avelumab concurrent with radiation therapy (end of cycle 4). Each cycle is 14 days. ]Quantitative immunohistochemical analysis of PD-L1 expression will be performed and correlated with treatment response. PD-L1 expression may be constitutive or inducible; radiation therapy has been demonstrated to induce the expression of PD-L1 on tumor cells(22). Tumor biopsy will be repeated during concurrent Avelumab/radiation treatment, and tumoral expression of PD-L1 analyzed.
- Quantification/characterization of tumor-infiltrating lymphocytes/PBMCs [ Time Frame: Blood samples will be obtained prior to treatment (baseline), after Avelumab monotherapy (post-cycle 1 treatment) following completion of Avelumab concurrent with radiation therapy (end of cycle 4). Each cycle is 14 days. ]To isolate TILs and collect PBMCs from this patient cohort according to the schedule in section 3.5.2 table 1.
- Characterization of tumoral MHC-I/II expression/ Analysis of MHC immunopeptidomes [ Time Frame: Tumor biopsies will be obtained prior to treatment (baseline), following Avelumab monotherapy (post-cycle 1 treatment) and following completion of Avelumab concurrent with radiation therapy. Each cycle is 14 days. ]The design of this study is such that pre- and post/during treatment biopsies can be compared for MHC antigen expression, hypothesizing that expression levels may have predictive value in the setting of checkpoint inhibition. Expression of MHC molecules (class I and class II) will be analyzed on pre- and post/during treatment biopsies by immunohistochemistry. In addition to quantifying tumoral expression of MHC I/II molecules at baseline, following treatment with Avelumab, and following treatment with Avelumab/RT, investigators propose small scale MHC class I immuno-isolation and peptide extraction(30) to determine the repertoire of antigenic peptides expressed at each of the three time-points. The investigators hypothesize that antigen quantity and diversity may have predictive value for response to Avelumab, and that treatment at each of the three time-points will alter the presentation of immunogenic antigens.
- Patient-reported quality of life: Brief Older People's Quality of Life questionnaire (OPQOL-brief) [ Time Frame: Assess patient-reported QoL at baseline and 30 days after last avelumab administration (cycle 5) ]
Brief Older People's Quality of Life questionnaire (OPQOL-brief) will be used to assess patient-reported QoL.
The OPQOL-BRIEF questionnaire has 13 items, with a preliminary single item on global QoL, shown below. This single item is not scored with the OPQOL; it is coded as Very good (1) to Very bad (5).
Each of the 13 items is scored Strongly agree=1, Agree=2, Neither=3, Disagree=4, Strongly disagree=5. The items are summed for a total OPQOL-Brief score, then positive items are reverse coded, so that higher scores represented higher QoL.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03737721
|Contact: John Walker, MD PhD FRCPC||780-432-8340||John.Walker2@ahs.ca|
|Contact: Alison Schmidtfirstname.lastname@example.org|
|Cross Cancer Institute||Recruiting|
|Edmonton, Alberta, Canada, T6G1Z2|
|Contact: John Walker, MD 780-432-8340|
|Principal Investigator:||John Walker, Walker||Alberta Health Services - Cross Cancer Institute|