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High Dose Ascorbic Acid and Nanoparticle Paclitaxel Protein Bound and Cisplatin and Gemcitabine (AA NABPLAGEM) in Patients Who Have Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT03908333
Recruitment Status : Withdrawn (Request to close per funding sponsor. Site not moving forward with trial.)
First Posted : April 9, 2019
Last Update Posted : May 30, 2019
Sponsor:
Collaborators:
Cancer Research UK
Stand Up To Cancer
Lustgarten Foundation
Destroy Pancreatic Cancer
Translational Genomics Research Institute
HonorHealth Research Institute
Information provided by (Responsible Party):
Ben George, Medical College of Wisconsin

Brief Summary:

The purpose of this study is to see if a combination of paclitaxel protein bound (also known as nab-paclitaxel), gemcitabine, and cisplatin when given with high dose Ascorbic Acid will be safe and effective in individuals with untreated metastatic pancreatic cancer.

Vitamin C is a nutrient found in food and dietary supplements. It protects cells and also plays a key role in making collagen (which provides strength and structure to skin, bones, tissues and tendons). High-dose vitamin C may be given by intravenous (IV) infusion (through a vein into the bloodstream) or orally (taken by mouth). When taken by intravenous infusion, vitamin C can reach much higher levels in the blood than when the same amount is taken by mouth. Some human studies of high-dose IV vitamin C in patients with cancer have shown improved quality of life, as well as improvements in physical, mental, and emotional functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss. Intravenous high-dose ascorbic acid has caused very few side effects in clinical trials.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Pancreatic Cancer Pancreas Cancer Pancreatic Adenocarcinoma Resectable Pancreatic Ductal Adenocarcinoma Pancreatic Metastasis Drug: Ascorbic Acid Drug: Paclitaxel protein-bound Drug: Cisplatin Drug: Gemcitabine Phase 1 Phase 2

Detailed Description:

Pancreatic cancer continues to be a very lethal disease. It was estimated that in 2016, 53,070 Americans would be diagnosed with pancreatic ductal adenocarcinoma (PDA), and 41,780 would die from the disease. This makes pancreatic cancer the third leading cause of death from cancer in the US.

PDA is the twelfth most common cancer in the world with 338,000 new cases diagnosed in 2012. It is estimated that worldwide there will be > 300,000 deaths from pancreatic cancer. Furthermore unfortunately PDA is projected to be the second leading cause of death from cancer in the US by 2030.

Detection of pancreatic cancer has notoriously been very late in the disease and therefore the 5-year survival rate is only 8%, which is actually a slight improvement over the last few years. Right now the only potential cure for pancreatic cancer is surgical resection (if the disease is caught early). However only about 20% of PDA patients are eligible for potentially curable resection and unfortunately most (> 80%) have recurrence of their cancer within 2 years of resection, and those recurrences are almost universally fatal.

Recently it has been shown that there are regimens that actually improve survival for patients with advanced stage IV PDA. Conroy and colleagues have developed the Folfirinox regimen, which in a large randomized trial improved survival over gemcitabine as a single agent. Von Hoff and colleagues developed the nanoparticle albumin (nab) associated paclitaxel plus gemcitabine regimen which improved survival over single agent gemcitabine. Even more recently Jameson and colleagues have presented a combined regimen of nab-paclitaxel + gemcitabine + cisplatin in a small 24 patient phase Ib/II trial which showed a response rate of 71% with 2 patients having complete response, a 1-year survival of 65% and a median survival of 16+ months.

While there have been multiple investigators and investigations into the use of ascorbic acid for patients with cancer (see ClinTrials.gov), its use has generally not been found to be of help for patients particularly when given orally - e.g. 10 grams daily.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IB/II Trial of High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have No Prior Therapy for Their Metastatic Pancreatic Cancer
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : May 1, 2023


Arm Intervention/treatment
Experimental: AA NABPLAGEM
ascorbic acid paclitaxel protein-bound cisplatin gemcitabine
Drug: Ascorbic Acid
25, 37.5, 56.25 or 75 grams/m2
Other Name: Vitamin C

Drug: Paclitaxel protein-bound
125mg/m2 over 30 minute IV infusions on days 1 and 8 repeated every 21 days

Drug: Cisplatin
25mg/m2 in 500 mL of NS over 60minute IV infusion on days 1 and 8 repeated every 21 days

Drug: Gemcitabine
1000mg/m2 in 500 mL over 30 minute IV infusion on days 1 and 8 repeated every 21 days




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 18 weeks ]
    To determine the maximum tolerated dose (MTD) of high dose ascorbic acid (AA) with triple therapy of nanoparticle paclitaxel protein bound + cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer

  2. Disease Control Rate [ Time Frame: 18 weeks ]
    CR+ PR+SD


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria [ Time Frame: 18 weeks ]
  2. Progression free survival (PFS) [ Time Frame: approximately 12 weeks from last study treatment ]
    Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression

  3. Changes in patient's self-reported quality of life: MD Anderson Symptom Inventory (MDASI-GI) [ Time Frame: 18 weeks ]
    Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)

  4. Changes in patient's self-reported pain levels: Brief Pain Inventory (BPI) [ Time Frame: 18 weeks ]
    Changes in patient's self-reported pain levels will be determined by administering the Brief Pain Inventory (BPI).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with measurable disease according to RECIST 1.1 criteria).
  • Adequate organ function.
  • Have a performance status of 0 or 1 on the ECOG performance scale.
  • Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving first dose of study medication.
  • Female participants of childbearing potential must be willing to use adequate method of contraception for the duration of the trial through one month after the last dose of trial treatment.
  • Male participants must agree to use adequate contraception for the duration of the trial through one month after the last dose of trial treatment.

Exclusion Criteria:

  • Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Only the following prior treatments in the adjuvant setting are permitted: gemcitabine and/or 5-FU or capecitabine or gemcitabine administered as a radiation sensitizer provided at least six months have elapsed since completion of the last dose and no lingering toxicities are present.
  • Palliative surgery less than four weeks prior to initiation of study treatment.
  • Exposure to any investigational agent within four weeks prior to initiation of study treatment.
  • Patients who need constant use of finger stick blood glucose monitoring for tight control of their diabetes being that the ascorbic acid causes false low readings of glucose via that technology.
  • Any person with a G6PD deficiency.
  • History of renal oxalate stones (if type of stone is unknown, need to assess urine oxalates level if >60mg/dL, then patient is not eligible for the study).
  • Patient is taking acetaminophen at any dose or any medication that contains acetaminophen within 72 hours of first dose of ascorbic acid.
  • Hypersensitivity to any of the agents proposed for treatment.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • For female participants: Is pregnant or breastfeeding or expecting to conceive within the projected duration of the trial, starting with the prescreening or screening visit through one month after the last dose of trial treatment.
  • For male participants: Is expecting to impregnate a sexual partner within the projected duration of the trial, starting with the prescreening or screening visit through one month after the last dose of trial treatment.
  • Patients with evidence of iron overload, defined as a transferrin saturation > 45 percent AND serum ferritin > 200 ng/mL (males) or >150 ng/mL (females).
  • Current, serious, clinically significant cardiac arrhythmias as determined by the investigator, or patient receiving a digitalis derivative.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03908333


Locations
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United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, California
University of California San Diego Moores Cancer Center
San Diego, California, United States, 92093
United States, Georgia
Piedmont Cancer Institute, PC
Atlanta, Georgia, United States, 30318
Piedmont Cancer Institute, PC
Fayetteville, Georgia, United States, 30214
Piedmont Cancer Institute, PC
Newnan, Georgia, United States, 30265
United States, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
Cancer Research UK
Stand Up To Cancer
Lustgarten Foundation
Destroy Pancreatic Cancer
Translational Genomics Research Institute
HonorHealth Research Institute
Investigators
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Principal Investigator: Ben George, MD Medical College of Wisconsin

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Responsible Party: Ben George, Associate Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT03908333     History of Changes
Other Study ID Numbers: PRO00034648
First Posted: April 9, 2019    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ben George, Medical College of Wisconsin:
metastatic pancreatic cancer
cancer
pancreatic
Vitamin C
Ascorbic Acid
Nanoparticle Paclitaxel Protein Bound
cisplatin
gemcitabine
pancreas
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Pancreatic Diseases
Adenocarcinoma
Carcinoma
Digestive System Diseases
Endocrine System Diseases
Vitamins
Ascorbic Acid
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites