Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Urinary Bladder Neoplasms

Genomic Instability

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Tumors from patient having muscle invasive bladder cancer who benefit from neoadjuvant chemotherapy with cisplatine included in VESPER cohort

Tumors from patient having muscle invasive bladder cancer who benefit from neoadjuvant chemotherapy with cisplatine included in Saint-Louis cohort

Tumors from patient having muscle invasive bladder cancer who benefit from neoadjuvant chemotherapy with cisplatine included in COBLAnCE cohort

Blood from patient having muscle invasive bladder cancer who benefit from neoadjuvant chemotherapy with cisplatine

neoadjuvant chemotherapy with cisplatine

Yves ALLORY, MD

This study will allow the investigators to better assess the efficiency of neoadjuvant chemotherapy before cystectomy by training a predictive model on different patient cohorts with bladder cancer.

The project is based on three prospective cohorts of patients with MIBC: the VESPER trial (n=296), the St-Louis Hospital cohort (n=99), and the COBLAnCE cohort (n=312). Using WES and RNAseq, the investigators will determine genomic instability, DDR gene mutation and molecular subtypes. After digitization of tumour slides, the investigators will train and test predictive models based on deep learning approaches to predict outcome after neoadjuvant chemotherapy, either by estimating molecular subtypes and genetic features from pathological images, or by directly defining a prognostic signature. The statistical analyses will assess the performance of the models combining genomic instability, DNA Damage Response mutations and/or molecular subtyping to predict outcome after neoadjuvant chemotherapy and compare them with the models based on WSI deep learning approaches. These results will help to design new therapeutic strategies.

Bladder Cancer and Neoadjuvant Chemotherapy Efficiency Before Cystectomy

Survival prEdiction in bLadder Cancer Patients Treated by nEoadjuvant Chemotherapy Before cysTectomy

The time from enrollment to progression or death

Institut Curie

University Hospital, Rouen

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Myotonic Dystrophy Type 1

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Trastuzumab

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

Atezolizumab

Alectinib

Ado-Trastuzumab Emtansine

Vemurafenib

Adenosine

Maytansine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Tyrosine Kinase Inhibitors

Tyrosine

MPDL3280A 1200mg IV infusion - 3 weekly until progression or unacceptable toxicity.

Or in combination with chemotherapy:

* For non-squamous: Cisplatin or Carboplatin plus pemetrexed \& MPDL3280A - 3 weekly for 4 cycles followed by MPDL3280A and pemetrexed 3 weekly until progression or unacceptable toxicity or completion of a total of 35 cycles. MPDL3280A will then continue 3 weekly until progression or unacceptable toxicity.
* For squamous: Carboplatin plus paclitaxel \& MPDL3280A - 3 weekly for 4 cycles followed by MPDL3280A 3 weekly until progression or unacceptable toxicity.

Trastuzumab emtansine (T-DM1) 3.6mg/kg - 3 weekly until PD IV infusion

Intravenous (IV) infusion, as monotherapy of in combination with chemotherapy

MPDL3280A

Powder for concentrate for solution for infusion

Trastuzumab emtansine

Charles Swanton

DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who relapse with NSCLC (clinical trials.gov ref. NCT02183883). .

The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal actionable mutation) is associated with PFS.

Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous or squamous).

Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib respectively.

DARWIN II will include extensive exploratory biomarker analysis to investigate a number of genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help guide future clinical trial design.

DARWIN II is an exploratory phase II study examining the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy.

It will examine how clonal dominance and intratumour heterogeneity influence outcomes after treatment, offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1. These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC. The relationship between intratumour heterogeneity and cfDNA/CTCs will also be explored in DARWIN II, which may develop tools for patient selection and monitoring to be examined further in future studies. Results from DARWIN II will help to identify a biomarker for anti-PD-L1 therapy which could be used for patient stratification in future phase III trials of molecules targeting this T-cell inhibitory checkpoint. DARWIN II will also provide preliminary data on efficacy of MPDL3280A, which could be used to design randomised studies.

This is a multicentre non-randomised phase II study based on patients with relapsed NSCLC, who have provided a biopsy sample at the time of relapse.

The study arms:

* Arm 1: Patients without an actionable mutation - MPDL3280A (atezolizumab) monotherapy or in combination with chemptherapy
* Arm 2: BRAFV600 - vemurafenib
* Arm 3: ALK/RET gene rearrangement - alectinib
* Arm 4: HER2 Amplification - trastuzumab emtansine

Arms 2-4 are closed to further recruitment as of 25th May 2021.

Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity

Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity - DARWINII

Defined as the period between the date of registration to the date of subsequent progression or death (whichever occurs first)

Investigator-assessed according to RECISTv1.1 and irRC (Arm 1 only)

Period between first complete response or partial response until the first date recurrence or progressive disease, assessed up to 84 months

Dose reductions, interruptions, modifications and exposure

Interrogation of recurrence and progression biopsies to decipher the molecular basis for resistance in combination with analyses of CTCs/cfDNA as well as CT imaging heterogeneity analyses

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Bladder Cancer and Neoadjuvant Chemotherapy Efficiency Before Cystectomy	NCT06294054	Bladder Cancer Genomic Instabi...	neoadjuvant che...	18 Years - 80 Years	University Hospital, Rouen
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity	NCT02314481	Non-small Cell ...	MPDL3280A Vemurafenib Alectinib Trastuzumab emt...	18 Years -	University College, London

Spots Global Cancer Trial Database for genomic instability