A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)

Phase 2

Active, not recruiting

• Conditions: Pancreatic Neoplasms; Cancer of the Pancreas; Cancer of Pancreas; Neoplasms, Pancreatic; Pancreas Neoplasms; Pancreas Cancer; Adenocarcinoma
• Interventions: Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: Pharmacological ascorbate

• Registration Number: NCT02905578
• Lead Sponsor: Joseph J. Cullen

Brief Summary

This clinical trial adds high-dose ascorbate (vitamin C) to the standard of care regimen for metastatic pancreatic adenocarcinoma (a type of pancreatic cancer). Subjects are randomized between a control group (standard treatment) and an intervention group (pharmacologic ascorbate in addition to the standard treatment).

Detailed Description

One of the standard treatments for metastatic pancreatic adenocarcinoma is nab-paclitaxel with gemcitabine. This standard therapy administers chemotherapy once per week for three weeks; patients then get a 'rest week' to complete the cycle (1 cycle = 4 weeks).

This study adds 75 grams of ascorbate (vitamin C, sometimes called pharamcological ascorbate because the dose is so high) to standard therapy. The ascorbate is administered intravenously - through a vein in the arm.

Participants in the control group will:

* receive gemcitabine and nab-paclitaxel chemotherapy, which is standard for their cancer.

* undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays

Participants in the intervention group will:

* receive 75 grams of ascorbate 3 times per calendar week for each week of the chemotherapy cycle.

* undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays

* provide blood samples to determine the biological effects, if any, the ascorbate has on the body during therapy.

This active therapy portion lasts until the disease progresses and a new treatment needs to be adopted - this can be months to years. If disease progresses, participants go back to standard follow-up for their caner and the new/additional therapy their doctors prescribe.

However, it is very important we remain in contact with participants; they will have life-long follow-up for this study.

Study Timeline

• Study First Submitted: 2016-09-14
• Study First Submitted QC: 2016-09-14
• Study First Posted: 2016-09-19
• Study Start: 2018-11-28
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-18
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

• Pathologic diagnosis (cell samples, biopsy, brushing, surgical sample) of adenocarcinoma of the pancreas. Cancer from the Ampullae of Vater is also eligible. The tissue sample can be from a metastatic location, like a lymph node.
• Metastatic or node positive disease
• One cancer site, that did not receive radiation therapy, that is at least 1 cm in size when looking at it by CT scan (CAT scan)
• Recommended to receive gemcitabine and nab-paclitaxel
• Failed initial therapy or be ineligible for definitive curative therapy (e.g., surgical excision, radiation therapy)
• A platelet count of at least 100,000 cells per mL
• A creatinine level of less than 1 1/2 times the upper limit of normal for the local lab test, or, a creatinine clearance of at least 60 mL/(min*1.73m2)
• Not pregnant
• Commit to using birth control during the study (all participants)

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Exclusion Criteria

• Prior chemotherapy to treat the metastatic disease

• Other therapy (including radiation) within the past 4 weeks

• Side effects from prior therapies that are still deemed moderate to severe by a physician

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

• Patients actively receiving insulin or who are currently recommended to receive insulin by a doctor

• Patients requiring daily finger-stick blood glucose measurements

• Patients who are on the following drugs and cannot have a substitution (or who decline the substitution):

  • warfarin
  • flecainide
  • methadone
  • amphetamines
  • quinidine
  • chlorpropamide

• An active cancer, other than the pancreatic cancer, that requires treatment.

• Enrolled in another therapeutic clinical trial

• Uncontrolled, intercurrent illness

• HIV positive individuals undergoing therapy due to known drug:drug interaction between antiretroviral drugs and high-dose ascorbate therapy

• Women who are nursing

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ascorbate group	nab-paclitaxel	Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks
Control	Gemcitabine	Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Each cycle has 1 rest week
Ascorbate group	Pharmacological ascorbate	Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks
Control	nab-paclitaxel	Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Each cycle has 1 rest week
Ascorbate group	Gemcitabine	Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks

Primary Outcome Measures

Name	Time	Method
Overall survival	Every 2 months for up to 20 years post-treatment	Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause.

Secondary Outcome Measures

Name	Time	Method
Tumor Response	Every 2 months for up to 10 years	Determine the objective response rate of the disease, assessed every 2 months using CT or MRI, and evaluated/defined using the RECIST criteria (v1.1). Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
Progression free survival	Every 2 months for up to 10 years	Time, measured in days, it takes disease to progress, where disease progression is defined by the RECIST criteria (v1.1). Timeframe is from radiation day 1 to date of disease progression.
Adverse event frequency and categorization	Monthly through 30 days after end of treatment.	Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE v4). Assessments will be monthly through 30 days past the end of therapy.

Trial Locations

Locations (1)

Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States