Prospective Phase I Study of GAX for Metastatic Pancreatic Cancer

NCT02581501 | Withdrawn Phase 1 DMC

• 1 other identifier: StamfordH
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

GAX represents a novel approach to the development of cancer chemotherapy agents in pancreatic cancer and is based upon extensive laboratory investigations for the induction of apoptosis in pancreatic carcinoma cells.

Conditions

Pancreatic Cancer

Keywords

Xeloda; Gemcitabine; Abraxane; Pancreatic Cancer; Metastatic Cancer; Phase I; 5-FU; Capecitabine; Gemzar; NAB-Paclitaxel; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Identification of Maximum Tolerated Dose and Dose Intensity in Patients with Pancreatic Cancer

  To determine the dose for Phase II study - identification of the maximum tolerated dose (MTD) and dose intensity in patients with advanced pancreatic cancer. As a Phase I study, primary objective is toxicity identification, not treatment efficacy.

  24 months

Secondary Outcomes (1)

• Progression Free Survival

  6 years

Other Outcomes (1)

• Assess Safety and Toxicity based upon NCI Common toxicity criteria version 4.1.

  24 Months

Study Arms (1)

Gemcitabine, ABRAXANE®, and Xeloda

EXPERIMENTAL

Level-1 ABRAXANE® 75 mg/m2 over 30 min Days 5 and 12 GEMCITABINE 600 mg/m2 over 60 min Days 5 and 12. XELODA 500 mg/m2 BID D 1-14 capped at total dose of 2000 mg/day Level 1 ABRAXANE® 100 mg/m2 over 30 min Days 5 and 12 GEMCITABINE 600 mg/m2 over 60 min Days 5 and 12 XELODA 500 mg/m2 BID D 1-14 capped at total dose of 2000 mg/day Level 2 ABRAXANE® 125 mg/m2 over 30 min Days 5 and 12 GEMCITABINE 600 mg/m2 over 75 min Days 5 and 12 XELODA 500 mg/m2 BID D 1-14 capped at total dose of 2000 mg/day Level 3 ABRAXANE® 125 mg/m2 over 30 min Days 5 and 12 GEMCITABINE 750 mg/m2 over 75 min Days 5 and 12 XELODA 500 mg/m2 BID D 1-14 capped at total dose of 2000 mg/day

Drug: GAX - Gemcitabine, Abraxane and Xeloda

Interventions

GAX - Gemcitabine, Abraxane and Xeloda DRUG

GAX represents a novel approach to the development of cancer chemotherapy agents in pancreatic cancer and is based upon extensive laboratory investigations for the induction of apoptosis in pancreatic carcinoma cells. It is our expectation that this combination will induce apoptotic pathways downstream of biochemical mechanisms of resistance and synergistically induce pathways for apoptosis that are non-p53 dependent, which have not been previously explored in chemotherapy trials for this cancer.

Also known as: Chemotherapy, Pancreatic Cancer

Gemcitabine, ABRAXANE®, and Xeloda

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of pancreas metastatic to any distant site. (Stage IV).
• Must have a lesion reproducibly measurable by CT or MRI scans per Recist 1.1 criteria
• Prior radiation and surgery allowed (except Target lesions) but GAX treatment should be: \>3 weeks since major surgery
• Bilirubin \< 1.5 mg/dL
• Patients must have adequate liver function: AST and ALT \< 2.5 X upper limit of normal, alkaline phosphatase \< 2.5 X upper limit of normal, unless bone metastasis is present (\<5 X upper limit of normal) in the absence of liver metastasis.
• Patients must have adequate bone marrow function: Platelets \>100,000, Hemoglobin \> 9.0g/dL and ANC \> 1,500
• Patients must have adequate renal function: creatinine \<1.5 mg/dL is recommended
• Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.
• Patients must have \< Grade 2 pre-existing peripheral neuropathy (per CTCAE)
• Clinical Parameters Life expectancy \> three months Age ≥ 18 years and ≤ 75 years Performance status 0-1 (ECOG) Pre-existing Peripheral Neuropathy (sensory) must be ˂ grade 2 Able to tolerate oral medications
• Informed Consent: Each patient must be completely aware of the nature of his/her disease process and must willingly give consent after being informed of the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.

You may not qualify if:

• Neuroendocrine cancer should be ruled out by histology or immunohistochemical staining of the specimen. Mixed histology, pancreatic neuroendocrine and adenocarcinoma tumors, will also be excluded.
• Prior chemotherapy is allowed, as long as less than or equal to two of the components of GAX were used previously for their treatment: this includes gemcitabine, capecitabine, 5-FU, or ABRAXANE® .
• Hypersensitivity: Patients with a history of severe hypersensitivity reaction to taxanes or other drugs formulated with polysorbate 80, or any of the other drugs in the GAX regimen are excluded.
• Serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g. serious infection) that would in the opinion of the investigator, increase the risk of serious neutropenic complications.
• Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity.
• Patients with compromised immune systems who are at increased risk of toxicity and lethal infections when treated with marrow-suppressive therapy.
• Serious cardiovascular thromboembolic disease, including: congestive heart failure NYHA class III or greater; unstable angina or new onset angina (starting within three months of screening for this protocol), or myocardial infarction within the past 3 months (prior to screening); serious cardiac arrhythmias requiring therapy; cerebrovascular accident including transient ischemic attacks within the past 3 months (prior to screening).
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis.
• Major surgery, open biopsy or significant traumatic injury within 3 weeks of receiving first study drug.
• Use of cytochrome P450 enzyme inducing drugs such as: antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital, but not Keppra), or St. John's Wort or rifampin (rifampicin).
• Prior malignancy in last 2 years other than curatively treated carcinoma in-situ of any site, non-melanoma skin cancer, or Stage I breast and/or bladder cancers (in situ), or early stage prostate cancer Stage I or II, curatively treated by surgery and/or radiation.

Sponsors & Collaborators

• Stamford Hospital: lead

Study Sites (1)

Stamford Hospital Bennett Cancer Center

Stamford, Connecticut, 06904, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

Albumin-Bound Paclitaxel; Capecitabine; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Anthony Gulati, M.D

  Stamford Hospital

  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 19, 2015
• First Posted: October 21, 2015
• Study Start: February 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 18, 2019

Record last verified: 2019-04

Locations

US (1)