Trial Title:
Copanlisib and Avelumab as a Maintenance Therapy for Advanced Bladder Cancer
NCT ID:
NCT05687721
Condition:
Advanced Urothelial Carcinoma
Conditions: Official terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Avelumab
Conditions: Keywords:
Urinary Bladder Neoplasms
Phosphatidylinositol 3-Kinase
immunotherapy
copanlisib
pembrolizumab
Ureteral Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single-arm study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
copanlisib
Description:
intravenous infusion (IV) at 60 mg on Day 1, 8 and 15 of each 4-week treatment cycle for
up to 26 cycles
Arm group label:
Therapeutic arm
Intervention type:
Drug
Intervention name:
Avelumab
Description:
800 mg intravenous infusion on Day 1 and 15 of each 4-week treatment cycle for up to 26
cycles
Arm group label:
Therapeutic arm
Summary:
Patients with metastatic bladder cancer are usually treated with chemotherapy. If their
cancers do not progress after chemotherapy, they can be enrolled into this study and
receive a standard-of-care immunotherapy medication named avelumab plus a study drug
named copanlisib.
Detailed description:
Patients with advanced urothelial cancer will be treated with platinum-based
chemotherapy. After chemotherapy, an imaging study will be performed to determine cancer
response. If there is no disease progression, patients will be eligible for this study.
After informed consent is obtained, patients are enrolled. The treatment include
immunotherapy avelumab as the standard of care plus a study medication copanlisib. Both
medications are administrated through intravenous infusion. Avelumab wil be given once
every two weeks while copanlisib will be administrated on Day 1, 8 and 15 of every 4-week
cycle. Patient will be followed up for disease progression.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female
2. Age > 18 years
3. Diagnosis:
1. Histologically or cytologically confirmed metastatic or recurrent urothelial
carcinoma. OR
2. Documented stage IV disease (T4b, Any N, M0; any T, Any N, M1a-b), or Stage
IIIB (T1-T4a, N2-N3, M0), or subset of stage IIIA (T1-T4a, N1, M0)
4. Completed prior first-line platinum-based chemotherapy at least 4 weeks and not more
than 10 weeks after the last dose of first line chemotherapy.
5. Patients without progressive disease as per RECIST v1.1 guideline (i.e., with an
ongoing CR, PR, or SD) following completion of the first-line chemotherapy.
6. Patient must be appropriate to receive Avelumab maintenance therapy
7. Measurable disease after chemotherapy is not required:
1. Patients must have had X-rays, CT/ MRI scans, PET or physical examinations
completed within 28 days prior to initial administration of study medications.
2. Patients may have no evidence of disease after platinum-based chemotherapy.
These patients will be included in the study for all other analyses except ORR
and irORR.
3. Soft tissue disease that has been radiated within two months prior to
registration is not assessable as measurable disease. Soft tissue disease that
has been radiated two or more months prior to registration is assessable as
measurable disease provided that the lesion has progressed following radiation.
As the biology of previously irradiated tumors may be different from
non-irradiated tumors, patients must have at least one measurable lesion
outside the previously irradiated region in order to be considered to have
measurable disease.
8. Tumor samples:
a.Provision of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block
from the most recent primary or metastatic tumor biopsy or resection obtained prior
to treatment with first line chemotherapy but within one year of enrollment, with no
intervening systemic anti-cancer therapy. If an FFPE tissue block cannot be
provided, 15 unstained slides (10 minimum) will be acceptable. If a suitable tissue
sample is not otherwise available, then a tissue from a de novo biopsy (core needle
or excisional) should have been obtained prior to initiation of this study. However,
this biopsy is not required for participation in this trial if he/she meets all
other inclusion and exclusion criteria. When patients undergo biopsy, in addition to
FFPE preparation, fresh tissue should be sent to VABHS for single-cell RNAseq and T
cell receptor sequencing as specified in the addendum.
9. Estimated life expectancy of at least 3 months.
10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) status 2 OR
Karnofsky Performance Status scale 60%. For the safety lead-in phase, only patients
with PS 0-1 will be included.
11. Adequate bone marrow function, including:
1. Leukocytes > 3000/mm3
2. Absolute neutrophil count (ANC) > 1,500/mm3
3. Platelets > 100,000/mm3
4. Hemoglobin > 9 g/dL (may have been transfused).
12. Adequate renal function, defined as estimated creatinine clearance 20 mL/minute as
calculated using the Cockcroft-Gault equation. It has been shown that creatinine
clearance 15 ml/minute did not significantly affect the pharmacokinetics of
copanlisib.
13. Adequate liver function, including:
b.Total serum bilirubin 1.5 x upper limit of normal (ULN) c.Aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) 2.5 x ULN d.Total serum
bilirubin < 3 x ULN for patients with Gilbert's syndrome or for patients with
cholestasis due to compressive adenopathy of the hepatic hilum
14. Serum pregnancy test (for females of childbearing potential) negative at screening.
15. Male patients able to father children and female patients of childbearing potential
and at risk for pregnancy must agree to use 2 highly effective methods of
contraception throughout the study and for at least 60 days after the last dose of
assigned treatment.
16. Evidence of a signed and dated informed consent document indicating that the patient
has been informed of all pertinent aspects of the study.
17. Patients who are willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other study procedures.
18. Controlled diabetes A1c < 8.5%. For patients with newly diagnosed diabetes mellitus
that cannot meet protocol requirements, a single rescreening (which includes all
screening procedures) should be performed when the patient's diabetes is controlled
and can meet protocol requirement for HbA1c).
19. Controlled arterial hypertension (per investigator assessment
Exclusion Criteria:
1. Patients whose disease progressed by RECIST v1.1 on or after first-line
platinum-based chemotherapy for urothelial cancer.
2. Patients who have had a major surgery within 4 weeks or major radiation therapy
within 2 weeks prior to randomization. Prior palliative radiotherapy is permitted,
provided it has been completed at least 48 hours prior to entering the study.
3. Patients who are receiving any other investigational agent within the preceding 4
weeks. Observational studies are permitted.
4. Prior treatment with a Phosphoinositide 3-kinase inhibitor.
5. Prior therapy with anti-PD1/PD-L1 monoclonal antibody for aBC. However, prior
treatment with adjuvant nivolumab is allowed if it was discontinued over 12 months
prior to the start of this trial.
6. Patients with known symptomatic central nervous system (CNS) metastases requiring
steroids. These patients have poor prognosis and often develop progressive
neurological dysfunction that would confound the evaluation of neurological and
other adverse events. Patients with previously diagnosed CNS metastases are eligible
if the participants have completed the treatment and have recovered from the acute
effects of radiation therapy or surgery prior to treatment, have discontinued
corticosteroid treatment for these metastases for at least 4 weeks, and are
neurologically stable.
7. Diagnosis of any other malignancy in past 3 years, except for adequately treated
basal cell or squamous cell skin cancer, other Stage 0 or Stage 1 cancers, or
incidental finding of prostate cancer during cystoprostatectomy.
8. Patients with symptomatic metastatic cancer, such as moderate to severe pain,
impaired organ function or spinal cord compression.
9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible.
10. Known severe hypersensitivity reactions to monoclonal antibodies (Grade > 3), any
history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of asthma
system controlled per the Global Initiative for Asthma 2015)
11. History or concurrent condition of interstitial lung disease of any severity and/or
severely impaired lung function (as judged by the investigator)
12. HbA1c > 8.5% at Screening
13. Known prior or suspected hypersensitivity to study drugs or any component in the
formulations.
14. Current or prior use of immunosuppressive medication within 7 days prior, except the
following:
1. Intranasal, inhaled, topical steroids, or local steroid injections (eg,
intra-articular injection)
2. Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or
equivalent
3. Steroids as premedication for hypersensitivity reactions (eg, CT scan
premedication)
15. Patient with a history or concurrent condition of Interstitial Lung Disease.
16. Patients with an active bleeding diathesis.
17. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
accident (<6 months prior to enrollment), myocardial infraction (<6 months prior to
enrollment), unstable angina, congestive heart failure (> New York Heart Association
Classification Class II), or serious cardiac arrhythmia requiring medication.
18. Active infection requiring systemic therapy.
19. Positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency
syndrome (AIDS) due to potential pharmacokinetic interactions with copanlisib.
20. 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 positive).
21. Other severe acute or chronic medical conditions including, but not limited to
pneumonitis; psychiatric condition including recent (within the past year) or active
suicidal ideation or behavior; or laboratory abnormality 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.
22. Vaccination within 4 weeks of the first dose of study treatment and while on trial
is prohibited except for administration of inactivated vaccines (for example,
inactivated influenza vaccine and COVID-19 vaccines).
23. Pregnant female patients, breastfeeding female patients, female patients of
childbearing potential and male patients who are unwilling or unable to use 2 highly
effective methods of contraception as outlined in the protocol for the duration of
the study and for at least 60 days after the last dose of investigational product
24. History of noncompliance to medical regimens.
25. Patients unwilling to or unable to comply with the protocol.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Address:
City:
Boston
Zip:
02130-4817
Country:
United States
Contact:
Last name:
Chong-Xian Pan, MD PhD
Phone:
857-203-6189
Email:
chong-xian.pan@va.gov
Investigator:
Last name:
Chong-Xian Pan, MD PhD
Email:
Principal Investigator
Start date:
November 1, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
VA Office of Research and Development
Agency class:
U.S. Fed
Collaborator:
Agency:
Bayer
Agency class:
Industry
Source:
VA Office of Research and Development
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05687721
