Patients in this intervention arm will receive the therapeutic combination of Alectinib dosed PO 600 mg bis in die (BID) with meals and Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

ALK Gene Rearrangement Positive

Non-Squamous Non-Small Cell Neoplasm of Lung

Alectinib dosed 600 mg twice a day (BID) with meals until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Alectinib

Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Bevacizumab

Instituto Nacional de Cancerologia

Alectinib in Combination With Bevacizumab in ALK Positive NSCLC

Phase II, Open Label, Single Arm Trial of Alectinib in Combination With Bevacizumab in Untreated and Previously Treated Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) With Positive ALK Driver Mutation

PFS based on response criteria according to RECIST 1.1 in untreated and previously treated patients with Advanced or metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab

To assess the ORR, based on response criteria according to RECIST 1.1, in untreated and previously treated patients with Advanced or Metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab.

To assess the brain ORR, based on response criteria according RECIST 1.1, in untreated and previously treated patients with Advanced or metastatic Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab.

To assess the OS in untreated and previously treated patients with Advanced or metastatic Non-Squamous ALK-rearranged NSCLC who receive treatment with Alectinib plus Bevacizumab.

To assess the time since inclusion until developing brain metastases in untreated and previously treated patients with Advanced or metastatic Non-Squamous ALK-rearranged NSCLC who receive treatment with Alectinib plus Bevacizumab.

To measure disease-related symptoms we will apply the Lung Cancer Symptom Scale (LCSS). The LCSS is designed as a disease-specific measure of quality of life particularly for use in clinical trials. It evaluates six major symptoms associated with lung mallignancies and their effect on overal symptomatic distress, functional activities, and global quality of life. The scale consists of two segments, one completed by the patient (9 items) and one completed by the health care professional (6 items). Scoring is assigned as follows: The patient scale consists of 9 visual analogue scales (100 mm horizontal line). Patient puts a mark on line to indicate intensity of response to the items in question (0 = lowest rating). The observer scale consists of a 5-point categorical scale (100=none; 75=mild; 50=moderate; 25=marked; 0=severe). The score is equal to the length of line marked by patient. An average of the aggregate score of all 9 items is the total score (0-100, 0= least symptom burden).

Oscar Gerardo Arrieta Rodríguez

Coordinator of the Thoracic Oncology Unit and Laboratory of Personalized Medicine

Instituto Nacional de Cancerologia de Mexico

Roche Pharma AG

Phase II, single arm trial assessing Alectinib in combination with Bevacizumab in untreated and previously treated patients with Advanced or Metastatic Non-Squamous ALK-rearranged NSCLC

ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
Treatment may continue for up to 34 cycles (103 weeks)

Soft Tissue Sarcoma

-Arginine deiminase (ADI) is a recombinant protein cloned from M. hominis, produced in E. coli, and conjugated with PEG of 20,000 mw using a succinimidyl succinate linker. Thus ADI-PEG 20 is an arginine degrading enzyme, ADI, coupled to PEG.

pegylated arginine deiminase

-Gemcitabine is a nucleoside metabolic inhibitor that exhibits antitumor activity.

Gemcitabine

-Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants.

Docetaxel

Up to 21 days prior to initiation of ADI-PEG 20 Day -1 (+/- 1 day as long as performed prior to initiation of gemcitabine.
Tumor biopsies are mandatory for the first 20 patients amendable to biopsy enrolled at Washington University only (completed as of 05/14/2019) and for all patients enrolled to the SCLC cohort

Tumor biopsy

-Day -7 (pre-treatment), Day -1, and Days 1 and 8 of each cycle

Research blood draw

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Stanford Medicine

Sarcoma Oncology Center

Washington University School of Medicine

Columbia University Medical Center

ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

A Phase II Trial of ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

PFS: defined as time on study to time patients progressed on the drug combination or death or latest follow-up if progression/death is not observed yet
Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

-OS: defined as time on study to time of death due to any reasons or latest follow-up (whichever is earlier)

CBR = proportion of patients who have experienced complete response (CR)+ partial response (PR) + stable disease (SD) lasting 24 weeks or longer
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

PEG- BCT-100 in patients with Leukaemia Starting dose 1600U/Kg IV infusion weekly

PEG- BCT-100 in patients with Neuroblastoma Starting dose 1600U/Kg IV infusion weekly

PEG- BCT-100 in patients with Sarcomas Starting dose 1600U/Kg IV infusion weekly

PEG- BCT-100 in patients with High Grade Gliomas Starting dose 1600U/Kg IV infusion weekly

Cancer

Pediatric Solid Tumor

Pediatric AML

Pediatric ALL

PEG- BCT-100

Women's & Children's Hospital

Birmingham Children's Hospital

Bristol Royal Hospital for Children

Addenbrookes Hospital

Royal Hospital for Children

Leeds Children's Hospital

Royal Manchester Children's Hospital

Royal Marsden Hospital

A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100)

A Phase I/II Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100) in Relapsed/Refractory Cancers of Children and Young Adults

Safety profile as measured by the occurrence/non-occurrence of DLT within 28 days of treatment with BCT-100.
o Optimal dose as measured by the complete depletion of arginine. This is defined as AAD <8μM arginine in the blood after 3 doses of BCT-100.

Disease response (Complete Response (CR) or Partial Response (PR)) after 8 weeks of treatment with BCT-100

Incidence and severity of Adverse Events (AEs) defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4

Disease response ( CR / PR) according to Cheson criteria

Disease response ( CR / PR) according to RECIST criteria

Disease response ( CR / PR) according to RANO criteria

Disease response ( CR / PR) according to INCR criteria

BCT-100 concentration in cerebrospinal fluid

arginine/саркома

Alectinib in Combination With Bevacizumab in ALK Positive NSCLC

ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100)

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