Overview

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers

Status:
Recruiting
Trial end date:
2023-04-16
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Southwest Oncology Group
Collaborator:
National Cancer Institute (NCI)
Treatments:
Albumin-Bound Paclitaxel
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Calcium
Calcium, Dietary
Camptothecin
Fluorouracil
Folic Acid
Immunoglobulins
Irinotecan
Leucovorin
Levoleucovorin
Paclitaxel
Ramucirumab
Criteria
Inclusion Criteria:

- Patients must have histologically or cytologically confirmed small bowel
adenocarcinoma. Ampullary adenocarcinomas are not eligible. Patients must have
metastatic disease or locally advanced unresectable disease

- Brain metastases are allowed if they have been adequately treated with radiotherapy or
surgery and stable for at least 30 days prior to registration. Patients must be
neurologically asymptomatic and without corticosteroid treatment for at least 7 days
prior to registration

- Patients must have measurable or non-measurable disease. All scans needed for
assessment of measurable disease must be performed within 28 days prior to
registration. Non-measurable disease must be assessed within 42 days prior to
registration. All disease must be assessed and documented on the Baseline Tumor
Assessment Form

- Patients must have progressed on prior therapy with a fluoropyrimidine and/or
oxaliplatin, given either for metastatic/locally advanced disease or as adjuvant
therapy completed within the previous 12 months

- Patients must have completed prior chemotherapy, immunotherapy, or radiation therapy
at least 14 days prior to registration and all toxicity must be resolved to grade 1
(with the exception of grade 2 neuropathy) prior to registration. In Common
Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 sensory neuropathy
is defined as "moderate symptoms; limiting instrumental activities of daily living
(ADLs)"

- Patients must have a complete medical history and physical exam within 28 days prior
to registration

- Patients must have a Zubrod performance status of 0 or 1

- Absolute neutrophil count (ANC) >= 1,500/mcL (must be obtained within 28 days prior to
registration)

- Platelets >= 100,000/mcL (must be obtained within 28 days prior to registration)

- A total bilirubin =< 1.5 x institutional limit normal (IULN) (must be obtained within
28 days prior to registration)

- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x
IULN (or 5.0 x IULN if liver metastases are present) (must be obtained within 28 days
prior to registration)

- Serum creatinine =< 1.5 x IULN OR calculated creatinine clearance >= 40 mL/min (must
have been obtained within 28 days prior to registration)

- Patient must have urinary protein =< 1+ on dipstick or routine urinalysis (UA) within
28 days prior to registration. If dipstick or routine analysis is >= 2+, a 24 - hour
urine collections for protein must demonstrate < 1000 mg of protein in 24 hours

- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial

- Patients must not have known dihydropyrimidine dehydrogenase deficiency

- Patients must be offered the opportunity to participate in specimen banking

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines

Exclusion Criteria:

- Patients must not have received prior treatment with irinotecan, taxane, or
ramucirumab for small bowel adenocarcinoma

- Patients must not have had major surgery within 28 days prior to registration, or
minor surgery within 7 days prior to registration, and must not be planned for
elective major surgery to be performed during protocol treatment

- Patients must not be currently enrolled in or have discontinued within the last 28
days a clinical trial involving an investigational product or non-approved use of a
drug, or concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study. Patients participating in
surveys or observational studies are eligible to participate in this study

- Patients must not be receiving chronic antiplatelet therapy, including dipyridamole or
clopidogrel, or similar agents

- Patient must not have a known bleeding diathesis

- Patient must not have uncontrolled or poorly-controlled hypertension (> 160 mmHg
systolic or > 100 mg HG diastolic for > 4 weeks) despite standard medical management

- Patient tumors must not have known deficient mismatch repair (dMMR) or microsatellite
instability high (MSI-H)

- Patients must not be pregnant or nursing and must have had a negative pregnancy test
within 4 weeks of starting treatment. Women/men of reproductive potential must have
agreed to use an effective contraceptive method. A woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months. In addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures

- Patients must not have an active infection requiring systemic therapy

- Patient must not have liver dysfunctions manifested by either (1) Child-Pugh B (or
worse) or (2) cirrhosis (any degree) and a history of hepatic encephalopathy or
clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites
is defined as ascites from cirrhosis requiring diuretics or paracentesis

- Patients must not have a history of deep vein thrombosis (DVT), pulmonary embolism
(PE), or any other significant thromboembolism (venous port or catheter thrombosis or
superficial venous thrombosis are not considered "significant") during the 90 days
prior to registration

- Patients must not have experienced any arterial thrombotic event (including but not
limited to myocardial infarction, unstable angina, stable angina markedly limiting
ordinary physical activity, cerebrovascular accident, or transient ischemic attack)
within 120 days prior to registration

- Patients must not have a prior history of gastrointestinal (GI) perforation/fistula or
other risk factors for perforation within 120 days prior to registration

- Patients must not have experienced any grade 3-4 GI bleeding within 90 days prior to
registration

- Patient must not have experienced any serious or non-healing wound, ulcer, or bone
fracture within 28 days prior to registration