Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Hyman Muss, MD

The primary purpose of this study is to measure the association between baseline expression of the senescence effector protein p16INK4a and myelosuppression due to chemotherapy in patients with breast cancer. Patients with Stage I-IV breast cancer will be included and myelosuppression will be assessed after the first cycle of chemotherapy via measurement of an absolute neutrophil count (ANC) measured one time between days 7-11 post cycle one. Study subjects will also be asked to complete a brief health behaviors questionnaire to gather information on other relevant variables.

Study of the P16 Gene as a Predictor of Myelosuppression in Breast Cancer Patients

LCCC 1027: Expression Of P16INK4a As A Predictor Of Myelosuppression In Patients With Breast Cancer

To measure and correlate baseline p16INK4a expression in subjects with stage I-IV breast cancer starting a new course of chemotherapy with a post cycle 1 chemotherapy absolute neutrophil count (ANC).

To explore the associations between p16INK4a expression at baseline and amount of vigorous physical activity, smoking habits, and weekly alcohol consumption.

To explore the associations between p16INK4a expression at baseline and other chemotherapy-related toxicities, including the maximum toxicity experienced during that course of chemotherapy.

To explore the associations between p16INK4a expression at baseline and type of chemotherapy received, co-morbidities, concomitant medications, and tumor characteristics.

UNC Lineberger Comprehensive Cancer Center

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Vitamins

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Regorafenib, 160 mg, PO, Days 4-10 and Days 18-24 of 28 day cycle

Regorafenib (BAY 73-4506)

FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

FOLFIRI

Placebo, 160 mg, PO, Days 4-10 and Days 18-24 of 28 day cycle

Placebo

Hanna Sanoff, MD

This randomized (2:1), multi-center, placebo-controlled, phase II efficacy study is designed to compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients with mCRC previously treated with a FOLFOX regimen.

This randomized (2:1 ratio), multi-center, placebo-controlled, phase II efficacy study is designed to compare progression-free survival (PFS) between regorafenib + FOLFIRI (5-fluorouracil + leucovorin + irinotecan \[ARM A\] versus placebo + FOLFIRI \[ARM B\]) in patients with metastatic colorectal carcinoma (mCRC) previously treated with a FOLFOX (5-fluorouracil + leucovorin + oxaliplatin) regimen. Secondary objectives include objective response (OR) rates, disease control (DC) rates, and overall survival (OS). A pharmacokinetic (PK) evaluation of irinotecan will be conducted in a subset of patients at selected sites. This trial also incorporates a number of exploratory analyses designed to evaluate potential correlations between blood and tissue biomarkers and clinical benefit.

Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer

Multi-Center, Randomized, Placebo-Controlled Phase II Study of Regorafenib in Combination With FOLFIRI Versus Placebo With FOLFIRI as Second-Line Therapy in Patients With Metastatic Colorectal Cancer

To compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

To compare overall response (OR) rates (OR= CR + PR) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

To compare Disease Control (DC) Rate (DC= CR + PR + SD) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions and Stable Disease (SD) ), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

To compare overall survival (OS) between ARM A and ARM B. OS is defined as the time from randomization until death as a result of any cause.

To compare the pharmacokinetic (PK) profile of FOLFIRI between a subset of patients receiving regorafenib (ARM A) and patients receiving placebo (Arm B). The Area Under the Curve (AUC) levels of the irinotecan metabolite SN-38 were compared.

Toxicity Assessments were made according to NCI CTCAE v. 4.0 . Severe events (grades 3-4) that occurred in a higher percentage of regorafenib treated participants as compared to placebo are reported below.

Bayer

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Arm A

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Arm B

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Ireland

Region of Enrollment

A scale by the Eastern Cooperative Oncology Group (ECOG) from 0-5 to describe patient's selfcare ability and activity level.

0, Fully active

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. Dead

ECOG Performance Status

Stages I, II, III indicate that cancer is present, and the higher the number the larger the cancer tumor and the more it has spread into nearby tissues. Stage IV indicates that cancer has spread to distant parts of the body.

Stage at diagnosis

Prior Biologic Agent

The 3 Ras genes in humans (HRas, KRas, and NRas) are the most common oncogenes in human cancer; some therapies are more effective with nonmutated wildtype genes.

Locally Reported RAS

Many mutations of the BRAF gene are associated with cancer. Some drugs are designed to work with mutated forms of the gene.

Locally Reported BRAF

Robin V. Johnson

Progression Free Survival (PFS)

Only evaluable participants (those who had RECIST measurements after baseline) were included in this analysis

Overall Response(OR)Rate

Disease Control (DC) Rate

Overall Survival (OS)

Cycle 1

Cycle 2

This objective was designed to only look at a small subset of participants (11 on each arm)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of the P16 Gene as a Predictor of Myelosuppression in Breast Cancer Patients	NCT01305954	Breast Cancer		18 Years -	UNC Lineberger Comprehensive Cancer Center
Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer	NCT01298570	Colorectal Canc...	Regorafenib (BA... FOLFIRI Placebo FOLFIRI	18 Years -	UNC Lineberger Comprehensive Cancer Center

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