Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Rare Diseases

Breast Neoplasms

Stomach Neoplasms

Liver Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Stomach Diseases

Liver Diseases

Stomach Cancer

Hematinics

All Drugs and Chemicals

Liver Extracts

Udo Rudloff, M.D.

Background:

* Researchers are trying to learn what causes certain types of cancer to spread to other organs in the body (metastasis). Cancer tumors may produce a very small number of specific cells (cancer stem cells) that cause the tumors to grow in other organs throughout the body.
* By examining cancer tumor tissue, normal tissue, blood, bone marrow, and other body fluids, researchers may determine whether these samples contain cancer stem cells. Cancer stem cells may provide information on whether the cancer will come back or spread before other routine x-ray studies or lab tests indicate its presence.

Objectives:

* To acquire a collection of solid organ cancer stem cells for future study.
* To analyze solid organ cancer stem cells from various types of cancer on a genetic level.
* To determine if solid organ cancer stem cells are present in the blood or bone marrow.

Eligibility:

* Patients 16 years of age and older who have solid organ cancer (cancer in the liver, colon, rectum, anus, pancreas, stomach, breast, skin, muscles, fat, connective tissue, uterus, ovary, cervix, vagina, vulva, or inner lining of the abdomen) or a precancerous growth, and who are scheduled to have a biopsy or surgery to remove the cancer as part of their treatment.

Design:

* This is a prospective trial designed to procure solid organ cancer stem cells before either surgery or biopsy.
* All patients registered to this trial will undergo surgery to extirpate their cancer in the NCI
* Prior to surgery or biopsy, 8 tablespoons of blood will be drawn.
* During the surgery or biopsy, a sample of normal tissue will be removed along with the cancerous or precancerous tissue. If separate consent is given, samples of bone marrow will also be taken.
* After discharge, patients will return to the clinic for routine visits every month for the first 3 months following surgery, and then about every 3 months for 2 years, and then every 6 months for 3 years. During the visits, patients will have routine blood and imaging studies done, and researchers will take additional blood samples (about 8 tablespoons at each visit) and optional bone marrow samples (4 teaspoons every 6 months) to be used for research.

Background:

* Traditional models of cancer metastasis posit that cancer metastases might originate stochastically in any cancer cell while, the Cancer-Stem-Cell hypothesis suggests that the metastasizing cells are Solid Organ Cancer Stem Cells (SOCSC).
* SOCSC are relatively resistant to current cancer therapies. Thus, effective treatment for metastatic cancers might require the targeting of SOCSC.
* Knowledge on SOCSC is chiefly derived from cell lines. However, data suggest vast differences between cell lines and SOCSC obtained from fresh tumors.
* This protocol is designed to facilitate fresh tissue procurement to study SOCSC.

Primary Objective:

-To study the natural history of SOCSC from various primary and metastatic solid organ cancers using established phenotypic and functional markers.

Secondary Objectives:

* To analyze SOCSC for potential targets that can be used to design novel cancer therapies that target cancer stem cells.
* To determine whether SOCSC are present in the blood and/or bone marrow, and study their quantitative and/or qualitative changes from time of surgical resection to time of recurrence and/or metastasis.
* To evaluate the potential of SOCSC and their quantitative and/or qualitative changes over time after surgery, to be used in future studies as biomarkers for the early detection of cancer recurrence and/or metastases.
* To collect detailed history, demographic, and treatment data as well as perioperative findings to evaluate potential correlation with the presence or absence of SOCSC.
* To develop an animal model to investigate potential interaction between bone marrow derived stem cells and solid organ cancers.
* To observe the course of normal stem cells over time in patients who had benign tumors that do not show evidence of cancer over time.
* To compare the course of normal stem cells with that of stem cells from patients with solid organ cancers.
* To specifically investigate families with clusters of cancer to determine if there is a relationship between SOCSC and potential familial genetic mutations specific to a particular cancer and if present, to compare these genetic abnormalities with individuals from the same family without cancer.

Eligibility:

* Patients 16 years of age or older with primary or metastatic solid organ cancers requiring resection or other cancer directed therapy that is deemed in the best interest of their cancer care.
* Patients with premalignant neoplasms who are scheduled to undergo surgery or biopsy as part of their diagnostic evaluation.
* Patients must have an ECOG performance score of 0-2.
* Patients must have laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to biopsy or surgery.

Design:

* This is a prospective trial designed to procure SOCSC from various benign and solid organ cancers tumors (primary or metastatic) and follow their natural history from time of surgery and or other cancer directed therapy to time of recurrence.
* SOCSC will be isolated using phenotypic and functional markers. Investigations will be performed on the following tissues: Blood prior and after surgery, tumor and adjacent normal tissue when available, bone marrow (strictly optional under separate consent), and peritoneal washings when applicable.
* After surgery blood will be drawn at 1 and 3 months and every 3-6 months thereafter during the follow-up period (5 years). Bone marrow may be analyzed every six months during the follow-up period (strictly optional).
* Patients will be followed with standard of care or other cancer directed therapy deemed in the best interest of the patient.
* It is anticipated that between 274 and 676 patients will be enrolled over a period of 5 years (2-5 patients per month).

The Natural History of Solid Organ Cancer Stem Cells (SOCSC)

National Cancer Institute (NCI)

Antineoplastic Agents

Panitumumab

Antineoplastic Agents, Immunological

Participants with advanced or metastatic CRC and with known mutation status and tumor harboring an oncogenic mutation of BRAF, KRAS, or NRAS and with documented disease progression by RECIST during or after at least 1 line of prior therapy will be enrolled into 4 planned sequentially run cohorts. Participants will receive escalating doses of BGB-3245 in combination with panitumumab to establish the MTD and RP2D by assessing the safety, tolerability, preliminary antitumor activity, and pharmacokinetics (PK) for the combination of BGB-3245 with panitumumab.

Participants with advanced or metastatic CRC that harbors KRAS or NRAS mutations who have been treated and had documented disease progression by RECIST criteria during or after at least 1 line of prior therapy. Participants will receive the RP2D of BGB-3245 in combination with panitumumab to further evaluate the safety, PK, and assess the preliminary antitumor activity of the RP2D of the BGB-3245 and panitumumab combination.

Participants with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) that harbors KRAS mutations who have been treated and had documented disease progression by RECIST criteria during or after at least 1 line of prior therapy. Participants will receive the RP2D of BGB-3245 in combination with panitumumab to further evaluate the safety, PK, and assess the preliminary antitumor activity of the RP2D of the BGB-3245 and panitumumab combination.

BGB-3245

Intravenous (IV) infusion via an infusion pump

MapKure

The primary objectives of Part 1 of this study are to:

* Assess the safety and tolerability of the combination of BGB-3245 and panitumumab in participants with advanced or metastatic colorectal cancer (CRC) with a known mutation status and tumor harboring an oncogenic mutation of v-Raf murine sarcoma viral oncogene homolog B; B-RAF proto-oncogene, serine/threonine kinase (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), or neuroblastoma RAS viral oncogene homolog (NRAS) with documented disease progression during or after at least 1 line of prior therapy.
* Determine the maximum tolerated dose (MTD) of BGB-3245 in combination with panitumumab and the recommended phase 2 dose (RP2D) of the combination.

The primary objective of Part 2 of this study is to determine the objective response rate (ORR) as assessed by initial investigator review using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with BGB-3245 and panitumumab combination treatment at the RP2D.

A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers

A Phase 1b, Open-Label, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 With Panitumumab in Patients With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers

MapKure, LLC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The Natural History of Solid Organ Cancer Stem Cells (SOCSC)	NCT00923052	Hepatic Cancer Pancreatic Duct... Colorectal Canc... Breast Cancer Gastric Cancer		16 Years - 100 Years	National Institutes of Health Clinical Center (CC)
A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers	NCT06194877	Colorectal Canc... Pancreatic Duct... Advanced or Met...	BGB-3245 Panitumumab	18 Years -	MapKure, LLC

Spots Global Cancer Trial Database for pancreatic ductal cancer