adult patients with stage IV cancer that are starting a new line of treatment

Twenty-five mL of peripheral blood (PB) will be collected for research. Blood will be collected in EDTA tubes and used to isolate ctDNA. For each subject we will request that he/she contribute 25 mL of plasma no more frequently than every 6 weeks, and at same time of standard of care blood draws and routine clinic visit, and for no more than 3 times (including baseline and end of study).

research blood draws

Antonio Giordano, MD

1. To demonstrate the ability to detect specific cancer mutations in ctDNA isolated from plasma of stage IV cancer patients at HCC.
2. To compare, in each patient, ctDNA longitudinal samples through treatment, and when available, with those of primary tumor and metastasis.

The overall goal of this study is to study circulating tumor DNA (ctDNA) in the blood to determine how cancer cells in patients react to treatment. DNA is short for deoxyribonucleic acid. DNA contains information that determines in part the traits, such as eye color, height, or disease risk, that are passed on from parent to child. This reaction will be measured by studying patient blood that will be collected before and during treatment until there is disease progression.

circulating tumor DNA (ctDNA) in the blood

Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC

Medical University of South Carolina

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Prostatic Neoplasms

Breast Neoplasms

Carcinoma, Renal Cell

Disease Progression

Disease Attributes

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

De novo tissue biopsy performed following disease progression

De novo tumor tissue biopsy

Blood biospecimens collected following disease progression

Research blood draws

Pfizer CT.gov Call Center

The TRANSLATE study aims to better understand why tumors become resistant to standard anti-cancer therapies.

New tumor biopsy and blood samples are collected after disease progression on standard-of-care anti-cancer treatment and compared to the initial (archival) tumor biopsy sample taken from the same patient.

Annotated reports of results from clinical Next Generation Sequencing (NGS) gene panel tests of both tumor and blood are sent directly from the testing lab to the study physician for discussion with the patient during the study.

Patients may participate in interventional treatment clinical trials at the same time as participating in the TRANSLATE study.

Primary data will be publicly available after the study to support further research.

Background: Development of new cancer treatments requires better understanding of why tumors develop resistance to standard-of-care (SOC) therapies. However, post-progression tumor biopsies are not routinely collected, limiting the tissue available to characterize mechanisms of treatment resistance. The TRANSLATE clinical study is specifically designed to address these critical gaps.

Trial design: TRANSLATE is a global, multicenter, translational study designed to collect and compare archival pre-treatment tumor tissue with paired de novo tumor and blood samples obtained following disease progression on SOC therapies, targeting therapeutically important areas of cancer biology.

Eligible Tumor Type and Most Recent SOC Therapy:

* Non-small-cell lung and Anti-PD-1/-L1 monotherapy
* Non-small-cell lung and Anti-PD-1/-L1 + platinum
* Clear cell renal cell carcinoma and Anti-PD-1/-L1 monotherapy
* Clear cell renal cell carcinoma and Doublet anti-PD-1/-L1 + anti-CTLA-4
* Clear cell renal cell carcinoma and Pembrolizumab + axitinib
* Clear cell renal cell carcinoma and Avelumab + axitinib
* HR+ HER2- breast and Palbociclib + hormonal therapy
* germline mutated BRCA breast and Olaparib or talazoparib monotherapy
* Castration-resistant prostate and Enzalutamide
* Castration-resistant prostate and Abiraterone + prednisone

Eligibility criteria include adults with locally advanced or metastatic tumors; radiographic evidence of progressive disease during the most recent SOC regimen; sufficient archival tumor tissue; and a post-progression tumor lesion that is safely accessible for a new biopsy.

The results from clinical NGS panel testing may help inform subsequent treatment plan or identification of relevant interventional clinical trials.

Patients are enrolled after disease progression on SOC and before change in treatment and participate in 3 study visits within approximately 3 months.

Next-generation sequencing results from analysis of tumor tissue and blood will be returned to the study physician and patient for review at a subsequent study visit within this timeframe.

The primary endpoint is the change in frequency of gene alterations between pre-treatment and post-progression tumor biopsies. Secondary endpoints address prioritized scientific hypotheses specific to each target area of biology and indication.

Primary data will be publicly available after the study to support further research.

Sponsored by Pfizer Inc.; EudraCT: 2018-003612-45.

Treatment Resistance Following Anti-cancer Therapies

TREATMENT RESISTANCE FOLLOWING ANTI-CANCER THERAPIES (TRANSLATE)

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Pfizer

Cholangiocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Gemcitabine

Oxaliplatin

Dexamethasone

Dexamethasone acetate

Floxuridine

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

All patients receive HAI FUDR (\[0.12 mg/kg/day kg 30\] / pump flow rate)\& dexamethasone ({1 mg/m2/day30} pump flow rate) on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) \& Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 \& 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, \& then every 2 weeks thereafter. Clinical MRI examinations of the abdomen \& pelvis are obtained at baseline following surgery, prior to treatment initiation \& 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 \& 9 thereafter A non-contrast CT of chest, abdomen \& pelvis will also be obtained as part of routine clinical care.

All patients receive HAI FUDR (\[0.12 mg/kg/day kg 30\] / pump flow rate)\& dexamethasone ({1 mg/m2/day 30}/ pump flow rate) on day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) \& Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 \& 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, \& then every 2 weeks thereafter. Clinical MRI examinations of the abdomen \& pelvis are obtained at baseline following surgery, prior to treatment initiation \& 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 \& 9 thereafter A non-contrast CT of chest, abdomen \& pelvis will also be obtained as part of routine clinical care.

All patients receive will receive gemcitabine alone with HAI FUDR/Dex Gemcitabine (800 mg/m2 IV over 30 minutes) alone on Days 1 and 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.

Floxuridine (FUDR)

dexamethasone

William Jarnagin, MD

The purpose of this study is to use both, liver pump treatment and systemic chemotherapy, to assess the effects this type of treatment has on the patient and the tumor. Liver pump treatment uses a metal pump that is surgically placed in the abdomen and gives chemotherapy directly to the liver. Systemic chemotherapy gives chemotherapy through a vein \[intravenously (IV)\] and treats the whole body. This type of treatment has been done before and had shown that people with both pump and systemic chemotherapy had improved results. The investigators hope that this combination of treatments improves the response to chemotherapy and reduces the spread of the disease.

Another purpose of this study is to learn the clinical importance of a specific type of MRI scan. The investigators would like to see if this type of MRI will help predict the response to the treatment and see if they could help the physician with their treatment plan. These scans will be done at specific time points.

The last purpose of this study is to learn more about how the tumor interacts with the chemotherapy. This will be done through a biopsy taken during surgery and blood draws at specific time points.

Permission from patients entering the study will be obtained to take normal and tumor liver biopsies at the time of surgery. These samples are voluntary and optional.

Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

A Phase II Study of Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

Treatment evaluation will be done using RECIST (version 1.1)

This study will investigate DCE-MRI as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.

This study will investigate diffusion weighted imaging (DWI) as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC	NCT03302325	Solid Tumor, Ad...	research blood ...	18 Years -	Medical University of South Carolina
Treatment Resistance Following Anti-cancer Therapies	NCT04436120	Disease Progres...	De novo tumor t... Research blood ...	18 Years -	Pfizer
Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)	NCT01862315	Intrahepatic Ch... Peripheral Chol... Cholangiolar Ca... Cholangiocellul...	Floxuridine (FU... dexamethasone Gemcitabine Oxaliplatin MRI Research blood ...	21 Years -	Memorial Sloan Kettering Cancer Center
Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC	NCT03302325	Solid Tumor, Ad...	research blood ...	18 Years -	Medical University of South Carolina
Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)	NCT01862315	Intrahepatic Ch... Peripheral Chol... Cholangiolar Ca... Cholangiocellul...	Floxuridine (FU... dexamethasone Gemcitabine Oxaliplatin MRI Research blood ...	21 Years -	Memorial Sloan Kettering Cancer Center

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