Metastatic Pancreatic CancerPhase 1/2NCT03908333
High Dose Ascorbic Acid and Nanoparticle Paclitaxel Protein Bound and Cisplatin and Gemcitabine (AA NABPLAGEM) in Patients Who Have Metastatic Pancreatic Cancer
A Phase 1/2 study testing Ascorbic Acid, Paclitaxel protein-bound and Cisplatin in people with Metastatic Pancreatic Cancer and Pancreatic Cancer, run by Medical College of Wisconsin at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Cancer, Pancreatic Cancer, Pancreas Cancer
- What is being tested?
- Ascorbic Acid, Paclitaxel protein-bound and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 6 sitesUnited States
- Study dates
- 1 May 2019to 1 May 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 17Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Piedmont Cancer Institute, PC
Atlanta, Georgia, 30318
Piedmont Cancer Institute, PC
Fayetteville, Georgia, 30214
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Piedmont Cancer Institute, PC
Newnan, Georgia, 30265
University of California San Diego Moores Cancer Center
San Diego, California, 92093
HonorHealth Research Institute
Scottsdale, Arizona, 85258
About this study
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
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.
Read the 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.
- Conditions
- Metastatic Pancreatic Cancer, Pancreatic Cancer, Pancreas Cancer, Pancreatic Adenocarcinoma Resectable, Pancreatic Ductal Adenocarcinoma, Pancreatic Metastasis
- Being tested
- Ascorbic Acid, Paclitaxel protein-bound, Cisplatin, Gemcitabine
- Keywords
- metastatic pancreatic cancer, cancer, pancreatic, Vitamin C, Ascorbic Acid, Nanoparticle Paclitaxel Protein Bound, cisplatin, gemcitabine, pancreas
- Medical subject headings
- Pancreatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic AcidDrug
Also called Vitamin C
25, 37.5, 56.25 or 75 grams/m2
Paclitaxel protein-boundDrug
125mg/m2 over 30 minute IV infusions on days 1 and 8 repeated every 21 days
CisplatinDrug
25mg/m2 in 500 mL of NS over 60minute IV infusion on days 1 and 8 repeated every 21 days
GemcitabineDrug
1000mg/m2 in 500 mL over 30 minute IV infusion on days 1 and 8 repeated every 21 days
| Study group | Role | What they receive |
|---|---|---|
| AA NABPLAGEM | Experimental | ascorbic acid paclitaxel protein-bound cisplatin gemcitabine Receives: Drug: Ascorbic Acid; Drug: Paclitaxel protein-bound; Drug: Cisplatin; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
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
Measured: 18 weeks
Disease Control Rate
CR+ PR+SD
Measured: 18 weeks
Secondary outcomes (4)
Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria
Measured: 18 weeks
Progression free survival (PFS)
Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression
Measured: approximately 12 weeks from last study treatment
Changes in patient's self-reported quality of life: MD Anderson Symptom Inventory (MDASI-GI)
Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)
Measured: 18 weeks
Changes in patient's self-reported pain levels: Brief Pain Inventory (BPI)
Changes in patient's self-reported pain levels will be determined by administering the Brief Pain Inventory (BPI).
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2019
- Study start1 May 2019 (estimated)
- Primary completion1 May 2022 (estimated)
- Study completion1 May 2023 (estimated)
Why it stopped: Request to close per funding sponsor. Site not moving forward with trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, Stand Up To Cancer, Lustgarten Foundation, Destroy Pancreatic Cancer, Translational Genomics Research Institute, HonorHealth Research Institute
- Responsible party
- Principal investigator, Ben George, Medical College of Wisconsin
- Investigators
- Ben George, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03908333
- Sponsor's protocol ID
- PRO00034648
- Status last verified
- May 2019
- First submitted
- 5 Apr 2019
- Last updated
- 30 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03908333
- Acronym / sponsor ID
- PRO00034648
- Conditions
- Metastatic Pancreatic Cancer, Pancreatic Cancer, Pancreas Cancer, Pancreatic Adenocarcinoma Resectable, Pancreatic Ductal Adenocarcinoma, Pancreatic Metastasis
- Keywords
- metastatic pancreatic cancer, cancer, pancreatic, Vitamin C, Ascorbic Acid, Nanoparticle Paclitaxel Protein Bound, cisplatin, gemcitabine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Request to close per funding sponsor. Site not moving forward with trial.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- Cancer Research UK, Stand Up To Cancer, Lustgarten Foundation, Destroy Pancreatic Cancer, Translational Genomics Research Institute, HonorHealth Research Institute
- Study start
- 1 May 2019 (estimated)
- Primary completion
- 1 May 2022 (estimated)
- Study completion
- 1 May 2023 (estimated)
- First posted
- 9 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine
| Arm | Type | Receives |
|---|---|---|
| AA NABPLAGEM | Experimental | Drug: Ascorbic Acid, Drug: Paclitaxel protein-bound, Drug: Cisplatin, Drug: Gemcitabineascorbic acid paclitaxel protein-bound cisplatin gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ascorbic AcidAlso: Vitamin C25, 37.5, 56.25 or 75 grams/m2 | Drug | AA NABPLAGEM |
| Paclitaxel protein-bound125mg/m2 over 30 minute IV infusions on days 1 and 8 repeated every 21 days | Drug | AA NABPLAGEM |
| Cisplatin25mg/m2 in 500 mL of NS over 60minute IV infusion on days 1 and 8 repeated every 21 days | Drug | AA NABPLAGEM |
| Gemcitabine1000mg/m2 in 500 mL over 30 minute IV infusion on days 1 and 8 repeated every 21 days | Drug | AA NABPLAGEM |
Primary outcome
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
Disease Control Rate
Time frame: 18 weeks
CR+ PR+SD
4 secondary outcomes
Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria
Time frame: 18 weeks
Progression free survival (PFS)
Time frame: approximately 12 weeks from last study treatment
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 pain levels: Brief Pain Inventory (BPI)
Time frame: 18 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2019.
Related trials for Metastatic Pancreatic Cancer
RecruitingPhase 1
A Study to Find a Suitable Dose of ASP5834 in Adults With Solid Tumors
Solid Tumor, Non-Small-Cell Lung Cancer
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08098488 in People With Advanced Solid Tumors.
Pancreatic Ductal Adenocarcinoma, Esophageal Cancer
RecruitingPhase 1/2
Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
Pancreatic Cancer, Renal Cell Cancer
Active, not recruitingPhase 2
Redefining FOLFIORINOX in Older Pancreatic Cancer Patients
Metastatic Pancreatic Cancer
RecruitingPhase 1
A Study of MGC026 in Participants With Advanced Solid Tumors
Advanced Solid Tumor, Advanced Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ben George, MD principal investigator
Medical College of Wisconsin
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ascorbic Acid, Paclitaxel protein-bound and Cisplatin in people with Metastatic Pancreatic Cancer and Pancreatic Cancer, run by Medical College of Wisconsin at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: 18 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2019.