Metastatic Pancreatic CancerPhase 1/2NCT03697239
High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + 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 Hitendra Patel at 1 site 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
- 1 siteUnited States
- Study dates
- Jun 2019to Dec 2022
- 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
Who cannot join
- 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
- 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
- Any person with a G6PD deficiency
- History of renal oxalate stones
Show all 11Show fewer
- Patient is taking acetaminophen at any dose, or any medication that contains acetaminophen within 72 hours of first dose of ascorbic acid.
- 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.
- Is pregnant or breastfeeding
- Current, serious, clinically significant cardiac arrhythmias or receiving a digitalis derivative.
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
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 (6)
Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria
Measured: 18 weeks
Percent of patients who normalize their CA19-9
Lab testing will be completed to evaluate normalization of CA19-19
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
Overall survival (OS)
Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine survival status
Measured: approximately 12 weeks from last study treatment
Changes in patient's self-reported quality of life
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
Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)
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 posted5 Oct 2018
- Study startJun 2019 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: FDA indicated the same study could not be conducted under multiple INDs
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
- Hitendra Patel
- 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
- Sponsor-investigator, Hitendra Patel, University of California, San Diego
- Investigators
- Hitendra Patel, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03697239
- Sponsor's protocol ID
- 181045
- Status last verified
- Jun 2019
- First submitted
- 21 Sep 2018
- Last updated
- 11 Jun 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 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
- NCT03697239
- Acronym / sponsor ID
- 181045
- 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: FDA indicated the same study could not be conducted under multiple INDs
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hitendra PatelUniversity, 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
- Jun 2019 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 5 Oct 2018 (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 (2 listed)
- Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with measurable disease according to RECIST 1.1 criteria).
- Adequate organ function
Key exclusion criteria (11 listed)
- 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
- 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
- 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
6 secondary outcomes
Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria
Time frame: 18 weeks
Percent of patients who normalize their CA19-9
Time frame: 18 weeks
Progression free survival (PFS)
Time frame: approximately 12 weeks from last study treatment
Overall survival (OS)
Time frame: approximately 12 weeks from last study treatment
Changes in patient's self-reported quality of life
Time frame: 18 weeks
Changes in patient's self-reported pain levels
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 11 Jun 2019.
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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.
Hitendra Patel, MD principal investigator
University of California, San Diego
1 site 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 Hitendra Patel at 1 site 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 2 inclusion and 11 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 11 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 11 Jun 2019.