Clinical trial NCT03797443: High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have Metastatic Pancreatic Cancer
Official title: Phase IB/II Trial of High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have Had No Prior Therapy for Their Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: Metastatic Pancreatic Cancer
Cancer
Pancreatic
Vitamin C
Ascorbic Acid
Paclitaxel Protein Bound
Cisplatin
Gemcitabine
Lead sponsor: Piedmont Cancer Institute
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Stand Up To Cancer
name: Lustgarten Foundation
name: Destroy Pancreatic Cancer
name: Translational Genomics Research Institute
First posted: 2019-01-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Be willing and able to provide written informed consent/assent for the trial.
* Be ≥ 18 years of age on day of signing informed consent.
* Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with measurable disease according to RECIST 1.1)
* Have a performance status of 0 or 1 on the ECOG performance scale.
* Demonstrate adequate organ function as defined below in Table 4, all screening labs should be performed within 21 days of treatment initiation.
* 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 (as outlined in section 4.4.2) for the duration of the trial through one month after the last dose of trial treatment.
* Male participants must agree to use adequate contraception (as outlined in section 4.4.2) for the duration of the trial through one month after the last dose of trial treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.

Exclusion Criteria:

* Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
* Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment.
* Exposure to any investigational agent within 4 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 (Vasudevan and Hirsch 2014) 39
* 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 pre-screening 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 pre-screening 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.

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: approx 63 days
measure: Disease control rate (CR+PR+SD x18 weeks)
timeFrame: approx 63 days
Secondary outcomes:
measure: Incidence of Treatment
timeFrame: 63 days
measure: Percent of patients who normalize their CA19-9
timeFrame: 63 days
measure: Overall survival (OS)
timeFrame: 12 weeks
measure: Progression free
timeFrame: approximately 12 weeks from last study treatment ]
measure: Changes in patient's self-reported quality of life
timeFrame: 63 days
measure: Changes in patient's self-reported pain levels
timeFrame: 63 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Fayetteville
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Newnan
country: United States
facility: Piedmont Cancer Institute
state: Georgia
Study officials:
References: