Pan FGFR Kinase Inhibitor BGJ398 and Combination Chemotherapy in Treating Patients With Untreated Metastatic Pancreatic Cancer

NCT02575508 | Withdrawn Phase 1 DMC

• 3 other identifiers: I 265214NCI-2015-01597P30CA016056
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the side effects and best dose of pan fibroblast growth factor receptor (FGFR) kinase inhibitor BGJ398 when given together with fluorouracil, irinotecan hydrochloride and oxaliplatin (combination chemotherapy) in treating patients with untreated pancreatic cancer that has spread to another place in the body. Pan FGFR kinase inhibitor BGJ398 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride 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 pan FGFR kinase inhibitor BGJ398 together with fluorouracil, irinotecan hydrochloride and oxaliplatin may be a better treatment for pancreatic cancer.

Conditions

Colon Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicity (DLT) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase Ib)

  Up to 28 days

• Maximum tolerated dose (MTD) and recommended phase II dose of BGJ398 in combination with mFOLFIRINOX, defined as the dose with a probability of DLT of 0.30 graded according to the NCI CTCAE version 4.0 (Phase Ib)

  The MTD will be estimated using isotonic regression (cumulative cohort design).

  28 days

• Overall survival (Phase II)

  The overall survival will be summarized using Kaplan-Meier methods, from which an estimate of the 6-month survival rate and corresponding standard error will be obtained using the methods proposed by Breslow and Day.

  Time from the start of the study treatment until death, last follow-up or drop-out, assessed at 6 months

Secondary Outcomes (5)

• Changes in CA19-9 expression levels (Phase II)

  Baseline to 2 years

• Incidence of adverse events graded according to the NCI CTCAE version 4.0

  Up to 28 days after completion of study treatment

• Objective tumor response (Phase II)

  Up to 2 years

• Progression free survival (Phase II)

  Up to 2 years

• Potential associations between response rate and tumor biomarkers (Phase II)

  Up to 2 years

Study Arms (1)

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

EXPERIMENTAL

Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously over 46 hours on days 1 and 15. Patients also receive pan FGFR kinase inhibitor BGJ398 PO QD on days 8-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Oxaliplatin; Drug: pan FGFR Kinase Inhibitor BGJ398; Other: Pharmacological Study

Interventions

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Actino-Hermal, Adrucil, Arumel, Cytosafe, Efudex, Efurix, Fiverocil, Fluoro Uracil, Fluoroplex, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Flurox, Ribofluor, Ro 2-9757, Ro-2-9757, Timazin

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, U-101440E

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

pan FGFR Kinase Inhibitor BGJ398 DRUG

Given IV

Also known as: BGJ398

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

Pharmacological Study OTHER

Correlative studies

Treatment (oxaliplatin, irinotecan, fluorouracil, BGJ398)

Eligibility Criteria

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

You may qualify if:

• Phase Ib: Histologically or cytologically confirmed adenocarcinoma of the pancreas, colon or rectum which disease is advanced (defined as not surgically curable) or metastatic in whom combination treatment using fluorouracil, oxaliplatin and irinotecan is a rational option
• All patients must consent to provide archival tumor samples; non-availability of evaluable tumor samples does not exclude patient from the study
• Phase II: Patients with histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma that have not received systemic chemotherapy for advanced or metastatic disease; the definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data
• Phase II: The initial 20 patients must have evaluable baseline tumor samples; evaluable samples are defined as those obtained by core biopsy or surgical resection and amendable to histological analysis; samples obtained by fine needle aspiration biopsy are not considered evaluable; patients who do not have evaluable archival tumor samples must consent to a tumor core biopsy prior to starting study treatment and, patients who consent to the baseline tumor biopsy will be eligible to receive study treatment irrespective of whether the samples obtained are evaluable
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Phase Ib: Have evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Phase II: Have at least 1 metastatic lesion other than the primary pancreatic tumor that is evaluable per RECIST 1.1 criteria; lesions previously irradiated are not considered evaluable
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (International System of Units \[SI\] units 1.5 x 10\^9/L)
• Platelets \>= 100,000 cells/mm\^3 (SI units 100 x 10\^9/L)
• Hemoglobin \>= 9.0 g/dL (SI units 90 g/L)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =\< 3 x ULN; in patients with known hepatic involvement, AST and ALT =\< 5 x ULN are allowed
• Serum creatinine =\< 1.5 x ULN or estimated creatinine clearance \>= 60 mL/min by the Cockcroft-Gault equation
• International normalized ratio (INR) =\< 1.5
• Inorganic phosphorus =\< ULN

You may not qualify if:

• Phase II: Patient who recurs with metastatic disease =\< 6 months of completing adjuvant chemotherapy after curative-intent surgical resection is not eligible; patients who recur with metastatic disease \> 6 months after completion of adjuvant chemotherapy are eligible
• Phase II: Patients that previously received systemic chemotherapy for metastatic or advanced pancreatic adenocarcinoma are not eligible
• Phase II: Diagnosis of any second malignancy within the last 3 years except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma or in-situ cervical carcinoma
• Patients with clinically significant ascites requiring paracentesis on 2 or more occasions within 4 weeks prior to start of study treatment
• Known hypersensitivity to BGJ398, fluorouracil, oxaliplatin, irinotecan or to any of the excipients
• Homozygous UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)\*28 (i.e. 7 TA repeats) gene alleles; the UGT1A1 test should be conducted per local institutional practice
• Palliative radiation treatment (e.g., pain control, bony lesions at risk of fracture) completed =\< 2 weeks of starting study treatment; patient will be eligible if palliative radiotherapy is completed \> 2 weeks from the start of study treatment and has recovered from radiotherapy toxicities
• Pulmonary embolus or thrombosis of the deep venous system (deep vein thrombosis \[DVT\]) within 2 weeks of starting study treatment; patients who had a history of thromboembolic disease should be stable on therapeutic anticoagulation using low molecular weight (LMW) heparin for at least 2 weeks prior to the start of study treatment; use of warfarin (or derivatives) is not allowed at the start of study treatment
• Patients with known symptomatic brain metastases requiring steroids and/or antiepileptic therapy; patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study treatment, and have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable; patients with leptomeningeal involvement are excluded
• Current evidence of corneal or retinal disorder/keratopathy including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination
• Prior FGFR inhibitor therapy
• History or current evidence of:
• Tissue calcification including, but not limited to, the soft tissue, kidneys, intestines, myocardium and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification
• Endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc
• Patients who are currently receiving or consuming

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Pancreatic Neoplasms

Interventions

Fluorouracil; dehydroftorafur; Irinotecan; Oxaliplatin; infigratinib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Study Officials

• Wen Wee Ma

  Roswell Park Cancer 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: October 6, 2015
• First Posted: October 14, 2015
• Primary Completion: May 1, 2020
• Last Updated: May 20, 2016

Record last verified: 2016-05

Locations

US (1)