Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Heart and Blood Diseases

Rare Diseases

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Nivolumab

Trastuzumab

Pertuzumab

Tucatinib

Axitinib

Bosutinib

Olaparib

Ipilimumab

Sirolimus

Palbociclib

Sunitinib

Dasatinib

Crizotinib

Erlotinib Hydrochloride

Temsirolimus

MTOR Inhibitors

Vemurafenib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tyrosine

CSF1R, PDGFRA, PDGFRB,VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, RET, FGFR1, FGFR2, FGFR3, VHL

AKT1, AKT2, AKT3, FBXW7, FLCN, mTOR, NF1, NF2, NTRK3, PIK3CA, PIK3R1, PTEN, RHEB, STK11, TSC1, TSC2

* Combination Phase - 3mg/kg nivolumab administered as an intravenous infusion over 30 minutes every 3 weeks for the first 4 doses in combination with ipilmumab 1mg/kg administered intravenously over 30 minutes, followed by the single-agent phase.
* Single-Agent Phase - 480mg nivolumab administered as an intravenous infusion over 30 minutes every 4 weeks.

Nivolumab plus Ipilimumab

125mg orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days

50mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off

25mg infused over a 30-60 minute period once a week

Erlotinib

Trastuzumab = 3-weekly dose schedule. The recommended initial loading dose is 8mg/kg administered as a 90-minute infusion followed by 3-weekly maintenance dose of 6mg/kg administered as 90-minute infusion.

Pertuzumab = 840mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 420mg administered over a period of 30-60 minutes.

Trastuzumab plus Pertuzumab

Vemurafenib = 960 mg orally every 12 hours.

Cobimetinib = 60 mg orally once daily for 21 days, followed by 7 days of rest

Vemurafenib plus Cobimetinib

Vismodegib

Janet Dancey

Quincy Chu

Daniel John Renouf

Francisco Vera-Badillo

Stephen Welch

John Hilton

Lillian Siu

Cristiano Ferrario

Kimberly Hagel

Sunil K. Yadav

Daniel J Renouf

Cancer drugs which target the effects of abnormal gene changes are called 'targeted therapies'. This study, called PM.1 or CAPTUR, will include some targeted therapies that are currently available. The purpose of this study is to find out what are the effects on a patient and their cancer when they are given a targeted therapy drug that is specific to an abnormal gene change in their cancer.

Recent advances in laboratory technology have enabled the identification of changes in the genetic makeup of tumors that might be responsible for their malignant behavior such as uncontrolled growth and spread. Some of these changes can be 'druggable', i.e. there may be cancer medicines that can specifically act on the tumour's genetic abnormality. Several cancer centers and programs have initiated this type of molecular profiling across Canada, with the goal to identify 'druggable' changes in tumors to find matching therapy for patients. These include initiatives in British Columbia, Ontario and Quebec. The CAnadian Profiling and Targeted agent Utilization tRial (CAPTUR) will test the activity of a list of commercially available targeted agents in patients who have undergone tumor profiling and have 'druggable' changes identified in their cancers.

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR): A Phase II Basket Trial

over the total number of patients in a given cohort.

AstraZeneca

Bristol-Myers Squibb

Hoffmann-La Roche

Pfizer

Seagen Inc.

Canadian Cancer Trials Group

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Melanoma

Urinary Bladder Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

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

Neuroendocrine Tumor

Neuroepithelioma

All eligible patients with melanoma will receive ipilimumab at a dose of 3 mg/kg combined with nivolumab at a dose of 1 mg/kg. The ipilimumab and nivolumab will be dosed every 3 weeks for 4 doses. Thereafter, patients may be eligible to continue to receive nivolumab monotherapy at a dose of 240 mg administered every 2 weeks OR nivolumab at dose of 480mg every 4 weeks for up to 2 years All eligible patients with bladder cancer will receive nivolumab at a dose of 240 mg administered every 2 weeks for up to 2 years, if the patient is clinically benefitting, the PI and treating investigator may elect to continue treatment beyond 2 years. All eligible patients with bladder cancer will receive nivolumab at a dose of 240 mg administered every 2 weeks for up to 2 years, if the patient is clinically benefitting, the PI and treating investigator may elect to continue treatment beyond 2 years.

Monotherapy Treatment - Nivolumab 240 mg flat dose Dosed q 2 weeks

OR

- Nivolumab 480 mg flat dose Dosed q 4 weeks

for up to 2 years from 1st dose of nivolumab or until loss of clinical benefit

Combination Treatment

* Ipilimumab 3 mg/kg
* Nivolumab 1 mg/kg Dosed q 3 weeks x 4 doses

Samuel Funt, MD

The purpose of this study is to investigate the characteristics of tumors in patients treated with nivolumab and to identify features that help to predict a good or bad response to this drug.

Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)

A Prospectively Designed Study to Assess the Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)

The primary clinical endpoint is response rate defined as the proportion of patients who achieve a complete or partial response based on RECIST criteria within 12 weeks of initiating treatment.

will be evaluated in pre-treatment and on-treatment biopsies. PD-L1 expression on tumor cells will be graded as positive or negative, according to the most up to date standards for the assay in use. PD-L1 expression on immune cells will be graded as \\ positive or negative, according to the most up to date standards for the assay in use (At present, \<5% staining is called negative whereas 5% or greater is considered positive).

UConn Health

Adaptive Biotechnologies

MedGenome

Memorial Sloan Kettering Cancer Center

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Nervous System Diseases

Eye Diseases

Lung Neoplasms

Recurrence

Strabismus

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gemcitabine

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months. Platinum-based chemotherapy will be given up to 6 cycles.

Platinum-based chemotherapy will be given up to 6 cycles. Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months.

Nivolumab will be administered at the standard dose of 360 mg every 3 weeks. Ipilimumab will be administered at the dose of 1 mg/kg every 6 weeks.

Nivolumab will be administered at the standard dose of 360 mg every 3 weeks.

Platinum-based chemotherapy will be chosen by the investigator among the following regimens:

* Cisplatin 80 mg/mq iv day 1 and Gemcitabine 1250 mg/mq iv days 1 and 8 every 21 days;
* Carboplatin AUC 5 iv day 1 and Gemcitabine 1000 mg/mq iv days 1 and 8 iv every 21 days;
* Carboplatin AUC 6 iv day 1 and paclitaxel 200 mg/mq iv day 1 every 21 days.

Platinum-based chemotherapy plus Nivolumab

Federico Cappuzzo

Angelo Delmonte, MD

Maximilian Papi, MD

Michele Aieta

Stefania Gori, MD

Sergio Bracarda

Francesco Grossi

Filippo De Marinis, MD

Fausto Barbieri, MD

Laura Bonanno, MD

Vittorio Gebbia

Vincenzo Minotti, MD

Federico Cappuzzo, MD

Francesca Zanelli, MD

Daniele Santini

Non-small-cell Lung Cancer (NSCLC) remains the leading cause of cancer death in Western Countries. Approximately 85% of lung cancers are of the non-small-cell type (NSCLC), with 25-30% of NSCLC being squamous histology type. Unlike nonsquamous NSCLC, squamous NSCLC rarely harbors epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations for which there are directed therapies, and until the recent approval of immunotherapies for pretreated squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. A platinum-based combination chemotherapy regimen has been the standard first-line treatment for all NSCLC. Carboplatin is frequently substituted for cisplatin for patients who have poor renal function or who experience toxicities from cisplatin (most notably, nausea and vomiting). Taxanes, especially paclitaxel, or vinorelbine or gemcitabine, commonly complete the standard two-drug backbone of platinum-based chemotherapy for the first-line treatment of NSCLC, with platin-gemcitabine as the most commonly used regimen in Europe in patients with squamous-histology. A recent press release announced that pembrolizumab plus chemotherapy produced higher response rate when compared to chemotherapy alone in patients with squamous-cell lung cancer. Nevertheless, no data on Progression-Free Survival (PFS) and Overall Survival (OS) are available. Therefore, considering the lack of data in patients with squamous histology and the lack of information about efficacy of combinations of immune-checkpoints inhibitors versus immune-checkpoint inhibitor plus chemotherapy, there is a strong rationale for conducting a study assessing efficacy of such strategies in patients with advanced, metastatic squamous-cell lung cancer.

Better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 (PD-1) and its ligand (PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. In the KEYNOTE 024 the anti-PD-1 inhibitor Pembrolizumab significantly prolonged progression-free survival (PFS) and overall survival (OS) of patients with advanced NSCLC and high PD-L1 level (\>50% of tumor cells) compared to platinum based chemotherapy, thus becoming a new standard of care in front line setting. However, the trial was not restricted to squamous population, with approximately 18% per arm having this histology. Nivolumab, another PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial comparing the drug to docetaxel, in second-line setting. Importantly, the benefit produced by the drug was irrespective of PD-L1 expression suggesting that the high mutation burden of squamous-cell lung carcinoma is more relevant than the expression of a single biomarker, at least in pretreated individuals. In addition, recent studies in chemo naive patients with non-squamous histology demonstrated that combination of chemotherapy and immunotherapy is superior to chemotherapy alone in terms of Overall Survival irrespective of PD-L1 expression (Keynote 189 and IMPOWER 150). In addition, the CheckMate 227 study recently showed that, in chemonaive NSCLC, combination of nivolumab and ipilimumab was superior to chemotherapy alone in patients with high tumor mutational burden (TMB), irrespective of PD-L1 expression. A recent press release announced that pembrolizumab plus chemotherapy produced higher response rate when compared to chemotherapy alone in patients with squamous-cell lung cancer (Keynote 407). Nevertheless, no data on Progression-Free Survival and Overall Survival are available. Therefore, considering the lack of data in patients with squamous histology and the lack of information about efficacy of combinations of immune-checkpoints inhibitors versus immune-checkpoint inhibitor plus chemotherapy, there is a strong rationale for conducting a study assessing efficacy of such strategies in patients with advanced, metastatic squamous-cell lung cancer.

An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)

SQUINT (Squamous Immunotherapy Nivolumab-Ipilimumab Trial): An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)

Overall Survival rate at 12 months in Arm A and B

Correlation of PD-L1 expression and/or TMB with outcome in Arm A and B

Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]

Clinical Research Technology S.r.l.

Fondazione Ricerca Traslazionale

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)	NCT03297606	Lymphoma, Non-H... Multiple Myelom... Advanced Solid ...	Olaparib Dasatinib Nivolumab plus ... Axitinib Bosutinib Crizotinib Palbociclib Sunitinib Temsirolimus Erlotinib Trastuzumab plu... Vemurafenib plu... Vismodegib Tucatinib	18 Years -	Canadian Cancer Trials Group
Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)	NCT02553642	Bladder Cancer Melanoma	Nivolumab Nivolumab plus ...	18 Years -	Memorial Sloan Kettering Cancer Center
An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)	NCT03823625	Squamous-Cell L...	Nivolumab plus ... Platinum-based ...	18 Years -	Fondazione Ricerca Traslazionale
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)	NCT03297606	Lymphoma, Non-H... Multiple Myelom... Advanced Solid ...	Olaparib Dasatinib Nivolumab plus ... Axitinib Bosutinib Crizotinib Palbociclib Sunitinib Temsirolimus Erlotinib Trastuzumab plu... Vemurafenib plu... Vismodegib Tucatinib	18 Years -	Canadian Cancer Trials Group
An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)	NCT03823625	Squamous-Cell L...	Nivolumab plus ... Platinum-based ...	18 Years -	Fondazione Ricerca Traslazionale

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