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

Joseph J. Cullen

Status and phase: Active, not recruiting; Phase 2

Conditions: Cancer of Pancreas; Neoplasms, Pancreatic; Pancreas Cancer; Adenocarcinoma; Cancer of the Pancreas; Pancreas Neoplasms; Pancreatic Neoplasms

Treatments: Drug: nab-paclitaxel; Drug: Gemcitabine; Drug: Pharmacological ascorbate

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02905578

3P30CA086862 (U.S. NIH Grant/Contract)

201801759

5U01CA140206 (U.S. NIH Grant/Contract)

P01CA217797 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 65 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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65 participants in 2 patient groups

Ascorbate group

Experimental group

Description:

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

Treatment:

Drug: Pharmacological ascorbate

Drug: Gemcitabine

Drug: nab-paclitaxel

Control

Active Comparator group

Description:

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

Treatment:

Drug: Gemcitabine

Drug: nab-paclitaxel