Phase I Trial of Combination of FOLFIRI and SOM 230

NCT01434069 | Completed Phase 1 DMC

• 2 other identifiers: MCC-16569SOM230CUS17T
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, phase I study of combination therapy with SOM 230 and FOLFIRI. We will utilize a sequential dose-escalation design to define the maximum tolerated dose (MTD) of SOM 230 when combined with standard doses of FOLFIRI.

Conditions

Gastrointestinal Tumor

Keywords

colon; rectum; small bowel; pancreas; gastric; esophageal; metastatic; unresectable; GI; combination therapy; dose escalation; solid tumor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose (using a standard 3+3 design), of SOM 230 and FOLFIRI.

  Average of 6 Months Per Participant

Secondary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  Average of 6 Months Per Participant

• Number of Participants With Tumor Response

  Average of 6 Months Per Participant

Study Arms (1)

Combination Therapy: FOLFIRI and SOM 230

EXPERIMENTAL

Treatment will be administered on an outpatient basis. FOLFIRI is administered by IV infusion every 2 weeks. The dose should be based on the patient's actual baseline body weight; the dose will be recalculated if there is a weight change of \> 10% from baseline. SOM 230 will be administered as an intramuscular dose determined by the dosing schema, every 28 days.

Drug: SOM230C LAR; Drug: FOLFIRI Infusion

Interventions

SOM230C LAR DRUG

Participants will be given one LAR dose injected into the muscle of the buttocks by a study nurse about once every 28 days until unacceptable toxicity or progression of the disease.

Also known as: Pasireotide LAR

Combination Therapy: FOLFIRI and SOM 230

FOLFIRI Infusion DRUG

Standard therapy of FOLFIRI

Also known as: 5-Fluorouracil (5FU), leucovorin (LV), and irrinotecan

Combination Therapy: FOLFIRI and SOM 230

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven metastatic/unresectable gastrointestinal malignancies (colon, small bowel, pancreas, gastric and esophageal cancer, etc.) not amenable to curative surgical therapy, for whom FOLFIRI can be considered a standard treatment
• Have had at least 1 prior treatment for all GI tumors except for small bowel adenocarcinoma as FOLFIRI can be considered standard first line therapy for that particular tumor.
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• ≥ 4 weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, Platelets ≥ 100 x 10\^9/L, hemoglobin (Hgb) \> 9 g/dL
• Adequate liver function as shown by: serum bilirubin ≤ 2 x upper limit of normal (ULN), and serum transaminases activity ≤ 3 x ULN
• Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating.
• Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information

You may not qualify if:

• Prior treatment with irinotecan. Irinotecan with radiation will be allowed if \> 4 weeks.
• Any cytotoxic chemotherapy, radiation, immunotherapy, or any investigational drug within the preceding 3 weeks of starting the study treatment
• History of liver disease, such as cirrhosis or chronic active hepatitis B and C
• History of, or current alcohol misuse/abuse within the past 12 months
• Known gallbladder or bile duct disease, ( ie infection or cholecystitis) acute or chronic pancreatitis
• Have undergone major surgery within 4 weeks prior to study enrollment
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Patients who have been treated at least 4 weeks prior to enrollment, and have a computed tomography (CT) scan or magnetic resonance imaging (MRI) of brain within 4 weeks of enrollment, which shows no evidence of progression of disease in brain, are allowed to enroll.
• Patients with uncontrolled diabetes mellitus defined as hemoglobin A1c (HbA1c) \>8% despite therapy or a fasting plasma glucose \> 1.5 ULN. Note: At the principal investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.
• Symptomatic cholelithiasis
• Have congestive heart failure: New York Heart Association (NYHA) Class III or IV and unstable angina
• History of syncope or family history of idiopathic sudden death
• Sustained or clinically significant cardiac arrhythmias including sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block (Mobitz II or higher atrioventricular nodal block AV)) , patients with prolonged corrected QT interval (QTc) (longer than 470 milliseconds) or a history of acute myocardial infarction within the 6 months preceding enrollment. (The "QT interval" is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. The "QTc" is the QT interval corrected for heart rate.)
• Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block
• Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism or cardiac failure
• Patients found to have sustained ventricular tachycardia, ventricular fibrillation, advanced heart block (Mobitz II or higher AV nodal block) , prolonged QTc (average longer than 470 milliseconds) in the holter monitor at the screening time. (this only applies to patients in cohorts of 60 mg of SOM 230 or higher)

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Digestive System Neoplasms; Neoplasm Metastasis

Interventions

Fluorouracil; Leucovorin; Irinotecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids

Study Officials

• Richard Kim, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2011
• First Posted: September 14, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 24, 2015

Record last verified: 2015-12

Locations

US (1)