Neoplasms

All Conditions

Rare Diseases

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Intestinal Adenocarcinoma

Small Intestine Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Irinotecan

Antibodies

Antibodies, Monoclonal

Paclitaxel

Leucovorin

Fluorouracil

Levoleucovorin

Albumin-Bound Paclitaxel

Calcium

Folic Acid

Camptothecin

Immunoglobulins

Calcium, Dietary

Ramucirumab

Lexatumumab

Vitamin B Complex

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Tubulin Modulators

Antimitotic Agents

Immunologic Factors

Hormones

Antimetabolites

Immunosuppressive Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Trace Elements

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Irinotecan Hydrochloride

Leucovorin Calcium

Christy Klepetko

Dana Sparks

Site Public Contact

Charles W. Drescher

John A. Ellerton

Jay W. Carlson

Gary L. Buchschacher

Christopher M. Reynolds

John M. Schallenkamp

Kendrith M. Rowland

Bryan A. Faller

Ardaman Shergill

Michael J Overman

This phase II trial studies how well ramucirumab and paclitaxel or the FOLFIRI regimen (leucovorin calcium, fluorouracil, and irinotecan hydrochloride) work in treating patients with small bowel cancers that have spread extensively to other anatomic sites (advanced) or are no longer responding to treatment (refractory). Ramucirumab is a monoclonal antibody that attaches to and inhibits a molecule called VEGFR-2. This may restrain new blood vessel formation therefore reducing nutrient supply to tumor which may interfere with tumor cell growth and expansion. Drugs used in chemotherapy, such as paclitaxel, leucovorin calcium, fluorouracil, and irinotecan hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Ramucirumab plus paclitaxel or FOLFIRI, may be helpful in treating advanced or refractory small bowel cancers and may help patients live longer.

PRIMARY OBJECTIVES:

I. To evaluate whether progression-free survival (PFS) meets an efficacy threshold in patients with previously treated advanced small bowel adenocarcinoma who receive treatment with ramucirumab and paclitaxel or FOLFIRI.

II. If the stated threshold is met in both arms, to choose the better regimen with respect to progression free survival (PFS).

SECONDARY OBJECTIVES:

I. To assess overall response rate (ORR) \[complete and partial, confirmed and unconfirmed\] in the subset of patients with measurable disease treated with ramucirumab and paclitaxel or FOLFIRI in this patient population.

II. To assess overall survival (OS) in patients treated with ramucirumab and paclitaxel or FOLFIRI in this patient population.

III. To evaluate safety and toxicity associated with combination ramucirumab and paclitaxel treatment or FOLFIRI therapy in this patient population.

TRANSLATIONAL OBJECTIVES:

I. To explore the correlation of maximum decrease in CEA levels and time to maximum decrease in CEA levels with PFS, OS, and ORR.

II. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients completing study treatment are followed up every 8 weeks until disease progression. Once the disease has progressed, patients are followed up every 6 months for up to 3 years post registration.

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers

Randomized Phase II Selection Study of Ramucirumab and Paclitaxel Versus FOLFIRI in Refractory Small Bowel Adenocarcinoma

CEA levels will be measured at the beginning of the first cycle and every 8 weeks during the study. Maximum decrease in CEA levels from treatment onset and time to maximum decrease in CEA will be summarized in descriptive analyses. Decrease in CEA levels will be defined as high (\>= 50% change) versus low (\< 50% change).

PFS will be assessed in all eligible and evaluable (received at least one dose of protocol therapy) patients using the Kaplan-Meier method, with statistical differences in event rates between treatment arms assessed via stratified Cox regression model.

Probabilities of OS will be estimated using the method of Kaplan-Meier, with statistical differences in event rates between treatment arms assessed via stratified Cox regression model.

Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Will be compared across treatment arms via chi-square tests.

Will be compared across treatment arms via chi-square tests.

National Cancer Institute (NCI)

SWOG Cancer Research Network

Capecitabine

Bevacizumab

Oxaliplatin

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Participants receive oxaliplatin via CVC over 2 hours and bevacizumab IV over 30-90 minutes on day 1. Participants also receive capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Michael Overman

This phase II trial studies how well bevacizumab given with capecitabine and oxaliplatin work in treating participants with small bowel or ampulla of Vater adenocarcinoma that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs using in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bevacizumab, capecitabine, and oxaliplatin may work better in treating participants with small intestinal or ampulla of Vater adenocarcinoma.

PRIMARY OBJECTIVES:

I. To determine the progression-free survival (PFS) at six months for patients with advanced adenocarcinoma of the small bowel (small intestine) or ampulla of Vater treated with capecitabine, oxaliplatin (CAPOX) and bevacizumab.

SECONDARY OBJECTIVES:

I. To determine the response rate (RR) for CAPOX and bevacizumab. II. To determine the overall progression free survival for CAPOX and bevacizumab.

III. To determine the overall survival (OS) for CAPOX and bevacizumab. IV. To determine the toxicity of CAPOX and bevacizumab.

OUTLINE:

Participants receive oxaliplatin via central venous catheter (CVC) over 2 hours and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Participants also receive capecitabine orally (PO) twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 10 and 30 days, and then every 3 months thereafter.

Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma

Phase II Study of Bevacizumab Combined With Capecitabine and Oxaliplatin (CAPOX) in Patients With Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater

A Bayesian sequential monitoring design will be used. PFS will be estimated using the Kaplan-Meier method.The length of time interval in months from date of first treatment, during and after the treatment a participant lives without progression.

Complete response + Partial response using RECIST 1.1 (Response Evaluation Criteria in Solid Tumor)

Time interval in months from date of first treatment until the date of first documented progression

The length of time interval in months from date of first treatment until the date of death or lost follow-up

Toxicity was graded according to the NCI Common terminology Criteria for Adverse Events (CTCAE) 4.0 except for neurosensory and skin toxicity. Neurosensory toxicity was graded according to the Neurologic Toxicity Scale for Oxaliplatin Dose Adjustments.

M.D. Anderson Cancer Center

Capecitabine 750mg/m2 oral twice daily, Days 1 - 14 and Panitumumab 9 mg/kg IV over 60 minutes on Day 1 and Oxaliplatin 130 mg/m2 IV over 2 hours Day 1 of 21-day cycle.

Bevacizumab + Capecitabine + Oxaliplatin

Capecitabine 750 mg/m2 oral twice daily, Days 1 - 14 and Bevacizumab 7.5 mg/kg IV over 90 minutes on Day 1 and Oxaliplatin 130 mg/m2 IV over 2 hours Day 1 of 21-day cycle.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Michael Overman/Gastrointestinal Medical Oncology

Number of Participants With Progression-free Survival (PFS) at Six Months

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unevaluable

Capecitabine 750mg/m2 oral twice daily, Days 1 - 14 and Bevacizumab 7.5 mg/kg IV over 90 minutes on Day 1 and Oxaliplatin 130 mg/m2 IV over 2 hours Day 1 of 21-day cycle.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers	NCT04205968	Metastatic Smal... Stage III Small... Stage IIIA Smal... Stage IIIB Smal... Stage IV Small ...	Fluorouracil Irinotecan Irinotecan Hydr... Leucovorin Leucovorin Calc... Paclitaxel Ramucirumab	18 Years -	SWOG Cancer Research Network
Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma	NCT01208103	Ampulla of Vate... Small Intestina... Stage III Ampul... Stage III Small... Stage IIIA Ampu... Stage IIIA Smal... Stage IIIB Ampu... Stage IIIB Smal... Stage IV Ampull... Stage IV Small ...	Bevacizumab Capecitabine Oxaliplatin	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stage iiib small intestinal adenocarcinoma ajcc v8