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

Primary Purpose

Metastatic Pancreatic Cancer, Pancreatic Cancer, Pancreas Cancer

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ascorbic Acid

Paclitaxel protein-bound

Cisplatin

Gemcitabine

About this trial

This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring metastatic pancreatic cancer, cancer, pancreatic, Vitamin C, Ascorbic Acid, Nanoparticle Paclitaxel Protein Bound, cisplatin, gemcitabine, pancreas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with measurable disease according to RECIST 1.1 criteria).
Adequate organ function

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
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
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.

Sites / Locations

UC San Diego Moores Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AA NABPLAGEM

Arm Description

ascorbic acid paclitaxel protein-bound cisplatin gemcitabine

Outcomes

Primary Outcome Measures

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

Disease Control Rate

CR+ PR+SD

Secondary Outcome Measures

Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria

Percent of patients who normalize their CA19-9

Lab testing will be completed to evaluate normalization of CA19-19

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

Overall survival (OS)

Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine survival status

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)

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)

Full Information

NCT ID

NCT03697239

First Posted

September 21, 2018

Last Updated

June 6, 2019

Sponsor

Hitendra Patel

Collaborators

Cancer Research UK, Stand Up To Cancer, Lustgarten Foundation, Destroy Pancreatic Cancer, Translational Genomics Research Institute, HonorHealth Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT03697239

Brief Title

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 No Prior Therapy for Their Metastatic Pancreatic Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Withdrawn

Why Stopped

FDA indicated the same study could not be conducted under multiple INDs

Study Start Date

June 2019 (Anticipated)

Primary Completion Date

December 2021 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Hitendra Patel

Collaborators

Cancer Research UK, Stand Up To Cancer, Lustgarten Foundation, Destroy Pancreatic Cancer, Translational Genomics Research Institute, HonorHealth Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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, pancreas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AA NABPLAGEM

Arm Type

Experimental

Arm Description

ascorbic acid paclitaxel protein-bound cisplatin gemcitabine

Intervention Type

Drug

Intervention Name(s)

Ascorbic Acid

Other Intervention Name(s)

Vitamin C

Intervention Description

25, 37.5, 56.25 or 75 grams/m2

Intervention Type

Drug

Intervention Name(s)

Paclitaxel protein-bound

Intervention Description

125mg/m2 over 30 minute IV infusions on days 1 and 8 repeated every 21 days

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD)

Description

Time Frame

18 weeks

Title

Disease Control Rate

Description

CR+ PR+SD

Time Frame

18 weeks

Secondary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria

Time Frame

18 weeks

Title

Percent of patients who normalize their CA19-9

Description

Lab testing will be completed to evaluate normalization of CA19-19

Time Frame

18 weeks

Title

Progression free survival (PFS)

Description

Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression

Time Frame

approximately 12 weeks from last study treatment

Title

Overall survival (OS)

Description

Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine survival status

Time Frame

approximately 12 weeks from last study treatment

Title

Changes in patient's self-reported quality of life

Description

Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)

Time Frame

18 weeks

Title

Changes in patient's self-reported pain levels

Description

Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)

Time Frame

18 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with measurable disease according to RECIST 1.1 criteria). Adequate organ function 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 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hitendra Patel, MD

Organizational Affiliation

University of California, San Diego

Official's Role

Principal Investigator

Facility Information:

Facility Name

UC San Diego Moores Cancer Center

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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