Last reviewed · How we verify

NCT03737123

Trial of Atezolizumab Plus Chemotherapy After Progression on PD-1 or PD-L1 in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma

Terminated Phase 2 Results posted Last updated 13 September 2023
What this trial tests

Phase 2 trial testing Carboplatin in Urothelial Carcinoma in 6 participants. Terminated before completion.

Timeline
19 December 2018
Primary endpoint
8 March 2022
18 May 2022

Quick facts

Lead sponsorNabil Adra
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment6
Start date19 December 2018
Primary completion8 March 2022
Estimated completion18 May 2022
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Nabil Adra

Who can join

18 and older, any sex, with Urothelial Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · From C1D1 until progression or death or up to a maximum of 26 months

Evaluate PFS among patients to be treated with atezolizumab in combination with carboplatin + gemcitabine or docetaxel, who have cisplatin-ineligible metastatic urothelial carcinoma and who have progressed on prior PD-1 or PD-L1 inhibitor. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause. Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment start

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.33.2 – NA
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Carboplatin + Gemcitabine or Docetaxel Secondary · From C1D1 until death or up to a maximum of 8 months

Assess the safety and tolerability of the combination of atezolizumab plus chemotherapy (carboplatin + gemcitabine or docetaxel) using CTCAE v4.03. Number of subjects who had any adverse events or events greater than grade 3 were reported in this outcome measure.

Number of patients had at least one adverse event of any grade
GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine6
Number of patients had at least one grade 3 or greater adverse event
GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine6
Number of patients had at least one grade 3 or greater treatment related adverse event
GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine6
Number of patients having serious adverse event
GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine3
Objective Response Rate (ORR) With RECIST 1.1 Secondary · From C1D1 until death or up to a maximum of 28 months.

Objective response rate (ORR) using RECIST 1.1 defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (O

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine405.3 – 85.3
Objective Response Rate (ORR) With irRECIST Secondary · From C1D1 until death or up to a maximum of 28 months.

ORR defined as the proportion of all subjects with confirmed PR or CR using immunerelated response criteria (irRECIST), from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per irRECIST for target lesions Complete Response (irCR), Disappearance of all target lesions; Partial Response (irPR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = irCR + irPR.

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine405.3 – 85.3
Clinical Benefit Rate (CBR) With RECIST 1.1 Secondary · From C1D1 until death or up to a maximum of 28 months.

Clinical benefit rate (CBR) of treatment (defined by proportion of all subjects with stable disease for at least 3 months, partial response, or complete response) using RECIST 1.1 from the start of treatment until disease/recurrence(taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine10047.8 – 100.0
Clinical Benefit Rate (CBR) With irRECIST Secondary · From C1D1 until death or up to a maximum of 28 months.

Clinical benefit rate (CBR) of treatment (defined by proportion of all subjects with stable disease for at least 3 months, partial response, or complete response) using irRECIST from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per irRECIST for target lesions: Complete Response (irCR), Disappearance of all target lesions; Partial Response (irPR), \>=30% decrease in the sum of the longest diameter of target lesions, neither sufficient shrinkage to qualify for irPR nor s

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine10047.8 – 100
PFS by irRECIST Secondary · From C1D1 until progression or death or up to a maximum of 26 months

PFS defined as duration from date of treatment start until progression according to irRECIST criteria or death from any cause. Per irRECIST criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.35.3 – NA
Overall Survival (OS) Secondary · From C1D1 until death or up to a maximum of 28 months

OS defined by the date of treatment start to date of death from any cause.

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + GemcitabineNA5.3 – NA
Progression Free Survival (PFS) Compared to Historical Controls Secondary · From C1D1 until progression or death or up to a maximum of 26 months

To compare Progression Free Survival(PFS) with the historical control, Null hypothesis - Patients receiving atezolizumab plus chemotherapy (carboplatin +gemcitabine or docetaxel) will have a median PFS of 4 months. Alternative hypothesis - Patients receiving atezolizumab plus chemotherapy (carboplatin + gemcitabine or docetaxel) will have a median PFS of 7.2 months. Progression Free Survival defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20%

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.33.2 – NA
Progression Free Survival (PFS) for Atezolizumab + Carboplatin and Gemcitabine Secondary · From C1D1 until death or progression or up to a maximum of 26 months

Evaluate PFS for atezolizumab + carboplatin and gemcitabine. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

GroupValue95% CI
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.33.2 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From C1D1 for every treatment cycle of 21 days until death or up to a maximum of 8 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase IIA : Atezolizumab + Carboplatin + Gemcitabine
Serious: 3/6 (50%)
Deaths: 1/6

Serious adverse events (5 terms)

ReactionSystemPhase IIA : Atezolizumab +…
ANEMIABlood and lymphatic system disorders
HYPERCALCEMIAMetabolism and nutrition disorders
STROKENervous system disorders
THROMBOEMBOLIC EVENTVascular disorders
URINARY TRACT INFECTIONInfections and infestations
Other adverse events (47 terms — click to expand)

ReactionSystemPhase IIA : Atezolizumab +…
ANEMIABlood and lymphatic system disorders
PLATELET COUNT DECREASEDInvestigations
ANOREXIAMetabolism and nutrition disorders
DIARRHEAGastrointestinal disorders
DIZZINESSNervous system disorders
DYSPNEARespiratory, thoracic and mediastinal disorders
FATIGUEGeneral disorders
NAUSEAGastrointestinal disorders
NEUTROPHIL COUNT DECREASEDInvestigations
PAINGeneral disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
PERIPHERAL SENSORY NEUROPATHYNervous system disorders
ABDOMINAL PAINGastrointestinal disorders
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
EDEMA LIMBSGeneral disorders
FEVERGeneral disorders
INFECTIONS AND INFESTATIONS - OTHER, SPECIFYInfections and infestations
LIPASE INCREASEDInvestigations
PRURITUSSkin and subcutaneous tissue disorders
RASH MACULO-PAPULARSkin and subcutaneous tissue disorders
THROMBOEMBOLIC EVENTVascular disorders
URINARY TRACT INFECTIONInfections and infestations
WHITE BLOOD CELL DECREASEDInvestigations
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
BACK PAINMusculoskeletal and connective tissue disorders
CHEST PAIN - CARDIACCardiac disorders
CONSTIPATIONGastrointestinal disorders
COUGHRespiratory, thoracic and mediastinal disorders
DEHYDRATIONMetabolism and nutrition disorders
DUODENAL ULCERGastrointestinal disorders
FALLInjury, poisoning and procedural complications
GENERALIZED MUSCLE WEAKNESSMusculoskeletal and connective tissue disorders
HEMATOMAVascular disorders
HEMATURIARenal and urinary disorders
HYPERCALCEMIAMetabolism and nutrition disorders
HYPERTENSIONVascular disorders
HYPOKALEMIAMetabolism and nutrition disorders
HYPONATREMIAMetabolism and nutrition disorders
HYPOTHYROIDISMEndocrine disorders
PANCREATITISGastrointestinal disorders

Most-reported serious reactions: ANEMIA, HYPERCALCEMIA, STROKE, THROMBOEMBOLIC EVENT, URINARY TRACT INFECTION.

Data from ClinicalTrials.gov NCT03737123 adverse events section.

Sponsor's own description

This is a single arm phase II study assessing the activity of atezolizumab in combination with carboplatin + gemcitabine or docetaxel compared to historical controls of chemotherapy only in metastatic or recurrent urothelial carcinoma subjects. Subjects that received a PD 1 or PD-L1 inhibitor with no prior platinum chemotherapy for metastatic disease will be treated with atezolizumab + carboplatin + gemcitabine on trial. Subjects that received sequential or concurrent PD1/PDL1 inhibitor and carboplatin-based regimen will be treated with atezolizumab + docetaxel on trial.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma.
    Mollica V, Rizzo A, Montironi R, Cheng L, et al · · 2020 · cited 75× · PMID 32498352 · DOI 10.3390/cancers12061449
  2. Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?
    Chocarro de Erauso L, Zuazo M, Arasanz H, Bocanegra A, et al · · 2020 · cited 58× · PMID 32317979 · DOI 10.3389/fphar.2020.00441
  3. Metastatic Urothelial Cancer: a rapidly changing treatment landscape.
    Stecca C, Abdeljalil O, Sridhar SS. · · 2021 · cited 40× · PMID 34616491 · DOI 10.1177/17588359211047352
  4. Current Status in Rechallenge of Immunotherapy.
    Hu H, Wang K, Jia R, Zeng ZX, et al · · 2023 · cited 35× · PMID 37215995 · DOI 10.7150/ijbs.82776
  5. Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review.
    Yang K, Li J, Sun Z, Zhao L, et al · · 2020 · cited 21× · PMID 33294036 · DOI 10.1177/1758835920975353
  6. Treatment Options for Metastatic Urothelial Carcinoma After First-Line Chemotherapy.
    Tassinari E, Mollica V, Nuvola G, Marchetti A, et al · · 2022 · cited 8× · PMID 35720644 · DOI 10.2147/cmar.s287904
  7. Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma.
    Patel A, Bisno DI, Patel HV, Ghodoussipour S, et al · · 2021 · cited 4× · PMID 34263255 · DOI 10.33696/cancerimmunol.3.047

Verify or expand the search:

Other trials of Carboplatin

Trials testing the same drug.

Other recruiting trials for Urothelial Carcinoma

Currently open trials in the same condition.

Other Nabil Adra trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03737123.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing