Trimodal Therapy Plus Atezolizumab in Muscle-invasive Bladder Cancer
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|ClinicalTrials.gov Identifier: NCT03620435|
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : August 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Safety Issues||Drug: Atezolizumab||Phase 2|
This will be a Phase II trial (stage 1 and 2). This study will initially accrue 3 evaluable patients to assess the dose limiting toxicity (DLT) of combination of Gemcitabine (4 weeks at 100 mg/m2, given intravenously once weekly, 2-4 hours before radiation therapy) plus IMRT (50 Gy/20 fractions. 2.5 Gy per fraction - 5 times per week for 4 weeks) and Atezolizumab (1200 mg intravenous on day 1 of 3 week cycle. Once the first 3 patients are accrued, the trial will be placed on hold for 3 months until acute toxicity has been assessed and the combination is felt to be safe according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE,v. 4.03). DLT will be defined as: (1) Grade 3 or higher immune related Adverse Events (irAEs), (e.g. inflammatory ocular toxicities, pneumonitis, hepatitis, colitis), (2) Grade 3 or higher treatment-related AEs (TRAE) that delay EBRT by > 21 days. For the safety run-in component of the study, 3 patients will receive Atezolizumab at a dose of 1200 mg every 3 weeks, as described above. After the third patient has been accrued, the trial will be placed on hold for 3 months for an assessment of acute toxicity. Acute toxicity is defined as any toxicity occurring within 90 days from the end of the combined treatment of IMRT and gemcitabine. If no grade 3 or higher acute toxicity is detected, Atezolizumab 1200 mg will be chosen for the rest of the trial. If one patient develops grade 3 toxicity, 3 further patients will be entered at 1200 mg. . If no further grade 3 toxicity is observed, this dose level will be considered safe. In case that one additional patient develop a grade 3 toxicity, then 3 patients will be enrolled at the reduced dose of 840mg. If no grade 3 or higher acute toxicity is detected, Atezolizumab 840mg will be chosen for the rest of the trial. If one patient develops grade 3 toxicity at the reduced dose, then 3 further patients will be entered at 840 mg. If no further grade 3 toxicity is observed, this reduced dose level will be considered safe. In case that one additional patient develop a grade 3 toxicity at the reduced dose level, it will be considered too toxic and the combination will be judged too toxic for the population and regimen, and the study will be terminated.
If treatment is well tolerated, this will be considered the final dose for the study. No further de-escalation beyond this level will be considered. For the Stage 2 of this study,, up to 22 other patients will be accrued (total of 25 evaluable patients). Atezolizumab will be given during combination treatment, and every 3 weeks for 16 cycles or until disease progression or unacceptable toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Transurethral Surgery Followed by a Combination of Atezolizumab (Tecentriq™) an Anti-PDL-1 (MPDL3280A) With Trimodal Therapy in Patients With Muscle-Invasive Bladder Cancer|
|Actual Study Start Date :||May 1, 2018|
|Estimated Primary Completion Date :||May 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Atezolizumab will be given during trimodal therapy, and every 3 weeks for 16 cycles or until disease progression or unacceptable toxicity.
Atezolizumab (1200mg iv, every 3 weeks) administered concurrently with TMT and adjuvant for up to one year
Other Name: Tecentriq
- Safety profile of intravenous Atezolizumab (anti-PDL-1) administered in combination with TMT in patients with MIBC [ Time Frame: 2-2.5 years ]Safety will be captured as (1) number of patients with Grade 3 or higher immune related Adverse Events (irAEs), (e.g. inflammatory ocular toxicities, pneumonitis, hepatitis, colitis), (2) number of patients with Grade 3 or higher treatment-related AEs (TRAE) that delay EBRT by > 21 days. The safety assessments up to the final follow-up visits will consist of monitoring and recording adverse events, including serious adverse events and adverse events of special interest, protocol−specified safety laboratory assessments, protocol−specified vital signs, and other protocol-specified tests that are deemed critical to the safety evaluation of the study.
- Overall survival [ Time Frame: 4 years ]OS is defined as the time from start of treatment to date of death due to any cause. Patients who have not died at the time of the analyses cutoff / end of study, will be censored at their last contact date known to be alive). Patient will be followed for 3 years from completion of radiotherapy
- Bladder cancer therapy impact on quality of life [ Time Frame: 2-2.5 years ]Changes from baseline quality of life will be measured longitudinally using the validated Functional Assessment of Cancer Therapy-Bladder questionnaire. FACT-BL scores on the first day of chemo radiotherapy treatment (before starting treatment), on the week 3 of radiation therapy, and again at 3, 6, 12, 18, and 24 months post radiation therapy. Quality of life domains measured includes domains of physical well-being, social and family well-being, emotional well-being, and functional well-being, as well as additional concerns specific to patients undergoing therapy for bladder cancer such as urinary, bowel and sexual function.
- Complete response to TMT combined with PDL-1 blockade [ Time Frame: 2-2.5 years ]LCR (loco-regional control rate) or early complete response rates from the combined therapy is the proportion of patients with a confirmed locoregional complete response at 3 months post-radiation. Loco regional complete response will be ascertained on basis of a combination of follow-up CT imaging of the irradiated field (bladder, pelvic lymph nodes), cystoscopy with rebiopsy of involved areas, and urine cytology.
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): NCT03620435
|Contact: Afsar Salimi, MSc||5149341934 ext email@example.com|
|Montreal, Quebec, Canada, H4A 3J1|
|Contact: Penny Chipman 514 934 1934 firstname.lastname@example.org|
|Study Chair:||Wassim Kassouf, MD||McGill University Health Center|