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

- DNA and RNA from blood - Stool samples for microbiome analysis - Urine samples for microbiome and general biomarker analysis - Saliva samples for microbiome and general biomarker analysis - Blood for general biomarker and metabolite profiling

Li-Fraumeni Syndrome

Hereditary Cancer Syndromes

TP53 Gene Germline Mutation Carrier

Scripps Clinic Medical Group

Biomarker Monitoring in TP53 Mutation Carriers

Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting

Laura Goetz

Staff Surgeon

Scripps Health

J. Craig Venter Institute

Single agent intravenous (IV) mithramycin

Single agent intravenous (IV) mithramycin
Mithramycin: 30 mcg/kg intravenous (IV) over 6 hours once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity.

Dose Level 1 - 30 mcg/kg Thoracic Malignancy

Dose Level 1 - 30 mcg/kg Extra Thoracic Malignancy

Single agent intravenous (IV) mithramycin
Mithramycin: 25 mcg/kg intravenous (IV) over 6 hours once daily for 7 days, to be repeated every 21 days (one cycle).

Dose Level -1 - 25 mcg/kg Thoracic Malignancy

Dose Level -1 - 25 mcg/kg Extra Thoracic Malignancy

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesion, 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 5mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Number of Participants With an Objective Response (Complete Response + Partial Response)

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Number of Participants With Serious and Non-Serious Adverse Events

Overall Study

Dr. David S. Schrump

Lung Cancer

Esophageal Cancer

Mesothelioma

Gastrointestinal Neoplasms

Breast Cancer

30 mcg/kg intravenous (IV) over 6 hours once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity

Mithramycin

National Institutes of Health Clinical Center, 9000 Rockville Pike

Mithramycin for Lung, Esophagus, and Other Chest Cancers

Phase II Evaluation of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum

alanine aminotransferase/sarcoma

Alectinib in Combination With Bevacizumab in ALK Positive NSCLC

Biomarker Monitoring in TP53 Mutation Carriers

Mithramycin for Lung, Esophagus, and Other Chest Cancers

Transfusion Safety Study (TSS)

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