Bladder CancerPhase 2NCT04579133
Neoadjuvant Durvalumab Alone Versus Durvalumab With Olaparib in Patients Ineligible for Cisplatin With Muscle-Invasive Urothelial Carcinoma of the Bladder Followed by Radical Cystectomy
A Phase 2 study testing Olaparib and Durvalumab in people with Bladder Cancer and Urothelial Carcinoma, run by Latin American Cooperative Oncology Group at 1 site in Brazil.
Trial summary
This study is a phase II, randomized, open-label, clinical trial including patients with muscle-invasive transitional cell carcinoma of the bladder candidates for radical cystectomy. The study will include patients ineligible for cisplatin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Urothelial Carcinoma
- What is being tested?
- Olaparib and Durvalumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Mar 2021to 1 Mar 2021
- 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
- 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- 2. Age > 18 years at time of study entry. 3. Evidence of muscle-invasive bladder cancer in a pretreatment transurethral biopsy sample.
- 4. All histologic subtypes (with exception of small-cell carcinoma) will be eligible if urothelial carcinoma was the predominant histopathologic feature.
- 5. Clinical stage T2-T4aN0M0 or T1-T4aN1M0 disease on imaging by American Joint Commission on Cancer, eighth edition.
- 6. Available primary tumor tissue (formalin-fixed paraffin embedded FFPE or slides) from transurethral biopsy/resection for biorepository.
- 7. Residual disease post transurethral resection prior to protocol inclusion and initiation.
Show all 21Show fewer
- 8. Patient must be planning to undergo a radical cystectomy at the time of randomization.
- 9. Unfit for cisplatin-based neoadjuvant chemotherapy defined as the presence of at least one of the characteristics below:
- Creatinine clearance less than 60 mL/min;
- Grade 2 or worse hearing loss;
- Grade 2 or worse neuropathy;
- New York Heart Association class III heart failure. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 11. Body weight >30kg 12. Adequate normal organ and marrow function as defined below:
- Haemoglobin ≥10.0 g/dL with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) 1.5 x 109/L
- Platelet count ≥100 x 109/L
- Total bilirubin ≤1.5 x institutional upper limit of normal (ULN).
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN 13. Evidence of post-menopausal status or negative urinary or serum pregnancy test prior to ICF signature for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- 14. Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non sterilized male partner must be in use of at least 1 highly effective method of contraception (see table in Section 7.1) before ICF signature/screening throughout the total duration of the drug treatment and the drug washout period (90 days after the last dose of durvalumab monotherapy). The study will not provide any method of contraception; this is responsibility of the patient in case of intention to participate in the study.
- 15. Male patients must use a condom during treatment and for 3 months after the last dose of study drug when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception. The study will not provide any method of contraception; this is responsibility of the patient in case of intention to participate in the study.
- 16. Patient is willing and able to comply with the protocol for the duration of the study, including undergoing treatment, scheduled visits, examinations and follow up.
Who cannot join
- Participation in another clinical study with an investigational product during the last 3 weeks.
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Any concurrent or within 3 weeks prior to study treatment systemic chemotherapy, IP, biologic, hormonal therapy or radiotherapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Patients must have recovered from any effects of any major surgery.
- History of allogenic organ transplantation or double umbilical cord blood transplantation (dUCBT).
- Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML
Show all 34Show fewer
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Curatively treated in situ cancer of the cervix
- Ductal carcinoma in situ (DCIS) of the breast
- Stage 1, grade 1 endometrial carcinoma
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia
- History of active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C (known positive HCV antibody) or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Screening for tuberculosis, hepatitis B, hepatitis C, and/or HIV infections is not required, unless there is clinical suspicion of these infections.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
- Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
- Patients who have received prior anti-PD-1, anti PD-L1, including durvalumab, or anti CTLA-4 antibodies.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Randomized Study of Neoadjuvant Durvalumab (MEDI4736) Alone Versus Durvalumab (MEDI4736) With Olaparib (AZD2281) in Patients Ineligible for Cisplatin With Muscle-Invasive Urothelial Carcinoma of the Bladder Followed by Radical Cystectomy
This study is a phase II, randomized, open-label, clinical trial including patients with muscle-invasive transitional cell carcinoma of the bladder candidates for radical cystectomy. The study will include patients ineligible for cisplatin.
Patients will be centrally randomized in a 1:1 ratio to receive durvalumab plus olaparib (Arm A) or durvalumab alone (Arm B).
The clinical study´s hypothesis is that for patients with muscle-invasive transitional cell carcinoma of the bladder who are not fit for cisplatin-based neoadjuvant chemotherapy, Durvalumab monotherapy will have a similar efficacy to historical chemotherapy controls and Durvalumab in combination with olaparib will be associated with an even improved efficacy results in terms of pathologic complete response (pCR).
- Conditions
- Bladder Cancer, Urothelial Carcinoma
- Being tested
- Olaparib, Durvalumab
- Keywords
- Bladder neoplasms, Bladder Cancer, Immunotherapy
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
300 mg BID OR 200 mg BID (if glomerular filtration rate [GFR] 31 to 50 mL/min)
DurvalumabDrug
Durvalumab 1500 mg IV
| Study group | Role | What they receive |
|---|---|---|
| durvalumab plus olaparib | Experimental | Durvalumab 1500 mg IV week 0, 3, 6 plus Olaparib tablets will be given orally on a continuous dosing schedule 300 mg BID OR 200 mg BID (if glomerular filtration rate [GFR] 31 to 50 mL/min) to complete 9 weeks of treatment. Receives: Drug: Olaparib; Drug: Durvalumab |
| durvalumab alone | Experimental | Durvalumab 1500 mg IV week 0, 3, 6 to complete 9 weeks of treatment Receives: Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response rate (pCR)
no evidence of invasive residual cancer (ypT0 or Tis/ypN0) in the surgical specimen.
Measured: 24 weeks
Secondary outcomes (5)
Overall Response rate (RR)
defined as proportion of patients with complete or partial response by RECIST v1.1.
Measured: 9 weeks
Pathological Response including Downstaging to Non-muscle-invasive Cancer in the Surgical Specimen (pPR)
defined as proportion of patients with pathological stage T1, Ta, and Tis.
Measured: 24 weeks.
Disease Free Survival (DFS)
defined as time from randomization to disease recurrence or death, whichever occur first.
Measured: 5 years.
Overall Survival (OS)
defined as time from randomization to death.
Measured: 5 years.
Safety (proportion of adverse events)
defined as proportion of patients with adverse events graded by CTCAE v5.0.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start1 Mar 2021
- Primary completion1 Mar 2021
- Study completion1 Mar 2021
Why it stopped: Not approved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Latin American Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04579133
- Sponsor's protocol ID
- LACOG 0219
- Status last verified
- Jun 2021
- First submitted
- 1 Oct 2020
- Last updated
- 16 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Study of Neoadjuvant Durvalumab (MEDI4736) Alone Versus Durvalumab (MEDI4736) With Olaparib (AZD2281) in Patients Ineligible for Cisplatin With Muscle-Invasive Urothelial Carcinoma of the Bladder Followed by Radical Cystectomy
- ClinicalTrials.gov ID
- NCT04579133
- Acronym / sponsor ID
- LACOG 0219
- Conditions
- Bladder Cancer, Urothelial Carcinoma
- Keywords
- Bladder neoplasms, Bladder Cancer, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not approved
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Latin American Cooperative Oncology GroupUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 8 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a phase II, randomized, open-label, clinical trial including patients with muscle-invasive transitional cell carcinoma of the bladder candidates for radical cystectomy. The study will include patients ineligible for cisplatin.
Patients will be centrally randomized in a 1:1 ratio to receive durvalumab plus olaparib (Arm A) or durvalumab alone (Arm B).
The clinical study´s hypothesis is that for patients with muscle-invasive transitional cell carcinoma of the bladder who are not fit for cisplatin-based neoadjuvant chemotherapy, Durvalumab monotherapy will have a similar efficacy to historical chemotherapy controls and Durvalumab in combination with olaparib will be associated with an even improved efficacy results in terms of pathologic complete response (pCR).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| durvalumab plus olaparib | Experimental | Drug: Olaparib, Drug: DurvalumabDurvalumab 1500 mg IV week 0, 3, 6 plus Olaparib tablets will be given orally on a continuous dosing schedule 300 mg BID OR 200 mg BID (if glomerular filtration rate [GFR] 31 to 50 mL/min) to complete 9 weeks of treatment. |
| durvalumab alone | Experimental | Drug: DurvalumabDurvalumab 1500 mg IV week 0, 3, 6 to complete 9 weeks of treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- 2. Age > 18 years at time of study entry. 3. Evidence of muscle-invasive bladder cancer in a pretreatment transurethral biopsy sample.
- 4. All histologic subtypes (with exception of small-cell carcinoma) will be eligible if urothelial carcinoma was the predominant histopathologic feature.
- 5. Clinical stage T2-T4aN0M0 or T1-T4aN1M0 disease on imaging by American Joint Commission on Cancer, eighth edition.
- 6. Available primary tumor tissue (formalin-fixed paraffin embedded FFPE or slides) from transurethral biopsy/resection for biorepository.
Key exclusion criteria (34 listed)
- Participation in another clinical study with an investigational product during the last 3 weeks.
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Any concurrent or within 3 weeks prior to study treatment systemic chemotherapy, IP, biologic, hormonal therapy or radiotherapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Patients must have recovered from any effects of any major surgery.
- History of allogenic organ transplantation or double umbilical cord blood transplantation (dUCBT).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaparib300 mg BID OR 200 mg BID (if glomerular filtration rate [GFR] 31 to 50 mL/min) | Drug | durvalumab plus olaparib |
| DurvalumabDurvalumab 1500 mg IV | Drug | durvalumab alone, durvalumab plus olaparib |
Primary outcome
Pathological complete response rate (pCR)
Time frame: 24 weeks
no evidence of invasive residual cancer (ypT0 or Tis/ypN0) in the surgical specimen.
5 secondary outcomes
Overall Response rate (RR)
Time frame: 9 weeks
Pathological Response including Downstaging to Non-muscle-invasive Cancer in the Surgical Specimen (pPR)
Time frame: 24 weeks.
Disease Free Survival (DFS)
Time frame: 5 years.
Overall Survival (OS)
Time frame: 5 years.
Safety (proportion of adverse events)
Time frame: 24 weeks
Results and safety
The study was stopped early (reason given: Not approved). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2021.
Related trials for Bladder Cancer
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
RecruitingPhase 3
A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)
Bladder Cancer
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Recruiting
Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Olaparib and Durvalumab in people with Bladder Cancer and Urothelial Carcinoma, run by Latin American Cooperative Oncology Group at 1 site in Brazil.
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 21 inclusion and 34 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: stopped early, as of the sponsor's last update on 16 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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 was stopped early (reason given: Not approved). Results are not available in the source record.
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 complete response rate (pCR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2021.