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Trial record 2 of 1612 for:    Pancreatic Cancer | United States

Prospective Phase I Study of GAX for Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT02581501
Recruitment Status : Withdrawn (Due to no enrollment, Celgene (sponsor) withdrew funding)
First Posted : October 21, 2015
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Stamford Hospital

Tracking Information
First Submitted Date  ICMJE October 19, 2015
First Posted Date  ICMJE October 21, 2015
Last Update Posted Date April 18, 2019
Actual Study Start Date  ICMJE February 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
Identification of Maximum Tolerated Dose and Dose Intensity in Patients with Pancreatic Cancer [ Time Frame: 24 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02581501 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
Progression Free Survival [ Time Frame: 6 years ]
To evaluate the response rate (using RECIST 1.1 criteria), the Progression free survival (PFS) and Overall Survival (OS) with treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 20, 2015)
Assess Safety and Toxicity based upon NCI Common toxicity criteria version 4.1. [ Time Frame: 24 Months ]
To assess the safety and toxicities to this regimen based upon NCI Common toxicity criteria version 4.1.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Prospective Phase I Study of GAX for Metastatic Pancreatic Cancer
Official Title  ICMJE Prospective Phase I Study of Gax (Gemcitabine, ABRAXANE, and Xeloda) for Metastatic Pancreatic Cancer Protocol # TSH - APG - 2015-01
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.
Detailed Description

It is the investigators 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. ABRAXANE® is novel in that it induces apoptosis to the same degree in mutant and wt p53 cancers. Mutant p53 tumors occur in 80-90% of PC and mutant p53 is thought of as one of the major mechanisms of drug resistance.

Furthermore, the investigators will be starting Xeloda and gemcitabine at slightly lower doses than the initial GTX studies. This is because the investigators have found that the efficacy is maintained at these slightly lower doses while side effects are minimized. The reason that GTX works at lower doses, as well as higher doses, is the synergy between drugs. Drug regimens that are synergistic can maintain their antitumor effect at doses lower than in non-synergistic regimens, but must maintain their dose intensity to achieve their anti-tumor effect. RECIST 1.1 criteria will be utilized for judging response, progression and stable disease. Overall assessment of the data will be by intention to treat analysis (ITT).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE Drug: GAX - Gemcitabine, Abraxane and Xeloda
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.
Other Name: Chemotherapy, Pancreatic Cancer
Study Arms  ICMJE Experimental: Gemcitabine, ABRAXANE®, and Xeloda

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

Intervention: Drug: GAX - Gemcitabine, Abraxane and Xeloda
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: December 5, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2015)
30
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed adenocarcinoma of pancreas metastatic to any distant site. (Stage IV).
  2. Must have a lesion reproducibly measurable by CT or MRI scans per Recist 1.1 criteria
  3. Prior radiation and surgery allowed (except Target lesions) but GAX treatment should be: >3 weeks since major surgery

    1. Bilirubin < 1.5 mg/dL
    2. 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.
    3. Patients must have adequate bone marrow function: Platelets >100,000, Hemoglobin > 9.0g/dL and ANC > 1,500
    4. Patients must have adequate renal function: creatinine <1.5 mg/dL is recommended
  4. Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.
  5. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE)
  6. 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
  7. 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.
  8. PT/PTT within normal or therapeutic limits as determined by the investigator. All subjects will be on Xeloda, use of warfarin is exclusionary.

Exclusion Criteria:

  1. 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.
  2. 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® .
  3. 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.
  4. 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.
  5. 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.
  6. Patients with compromised immune systems who are at increased risk of toxicity and lethal infections when treated with marrow-suppressive therapy.
  7. 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).
  8. Serious non-healing wound, ulcer, or bone fracture.
  9. Evidence or history of bleeding diathesis.
  10. Major surgery, open biopsy or significant traumatic injury within 3 weeks of receiving first study drug.
  11. 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).
  12. 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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02581501
Other Study ID Numbers  ICMJE StamfordH
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Stamford Hospital
Study Sponsor  ICMJE Stamford Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anthony Gulati, M.D Stamford Hospital
PRS Account Stamford Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP