Ph 2 Trial of Vitamin C & G-FLIP (Low Doses Gemcitabine, 5FU, Leucovorin, Irinotecan, Oxaliplatin) for Pancreatic Cancer

NCT01905150 | Completed Phase 2 Results

• 1 other identifier: 119005
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer, especially at advanced metastatic stage, is a devastating disease. It is the fourth leading cause of cancer death. Its prognosis is grim - 5-year survival rate being 6%. The current therapies for advanced metastatic pancreatic cancer are very toxic and with limited efficacy. A safer and more effective therapy for this devastating disease is greatly needed. G-FLIP regimen is a combination of low doses (doses lower than those approved by the FDA and used in the clinic) of several anti-cancer drugs, Gemcitabine, Fluorouracil, Leucovorin, Irinotecan and Oxaliplatin. The efficacy of G-FLIP against cancers (especially pancreatic cancer) is based on laboratory and clinical results, which indicates the synergistic efficacy of these anti-cancer drugs against cancer cells and overcoming tumor drug resistance that cancer cells frequently develop. Also, because of their low doses, this regimen is less toxic than when these drugs are used alone. Meanwhile, intravenous infusion of high doses (doses significantly higher than the daily nutritional requirements) of Vitamin C (ascorbic acid) has been observed to have anti-cancer activities. This is especially true when Vitamin C is used in combination with other anti-cancer drugs.

Conditions

Pancreatic Cancer

Keywords

pancreatic Cancer; G-FLIP, Gemcitabine 5FU Leucovorin Irinotecan Oxaliplatin; G-FLIP-DM (G-FLIP + Low doses Docetaxel and Mitomycin C); Vitamin C (ascorbic acid)

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Mean months subjects survived.

  Survival was monitored from the first day of treatment until the date of death or last followed up.

Secondary Outcomes (1)

• Objective Response

  Performed before the start of treatment, at the beginning of each 2-week treatment cycle, at follow-up visit two weeks after completion of treatment, and for up to 3 years after the start of treatment.

Other Outcomes (2)

• Quality of Life Questionnaire

  Performed before the start of treatment, at the beginning of each 2-week treatment cycle, and at follow-up visit two weeks after completion of treatment.

• Adverse Events

  Performed before the start of treatment, at the beginning of each 2-week treatment cycle, and at follow-up visit two weeks after completion of treatment.

Study Arms (2)

G-FLIP+VitaminC, then G-FLIP-DM+VitaminC

EXPERIMENTAL

G-FLIP in combination with Vitamin C, then G-FLIP-DM in combination with Vitamin C

Drug: G-FLIP; Drug: G-FLIP-DM; Dietary Supplement: Vitamin C

G-FLIP, then G-FLIP-DM

ACTIVE COMPARATOR

G-FLIP alone, then G-GLIP-DM alone

Drug: G-FLIP; Drug: G-FLIP-DM

Interventions

G-FLIP DRUG

G-FLIP is a combination of Low Doses of Gemcitabine, Fluorouracil \[5FU\], Leucovorin, Irinotecan, and Oxaliplatin

Also known as: Low doses of Gemcitabine, Low dose Fluorouracil [5FU], Leucovorin, Low dose Irinotecan, Low dose Oxaliplatin)

G-FLIP+VitaminC, then G-FLIP-DM+VitaminC; G-FLIP, then G-FLIP-DM

G-FLIP-DM DRUG

G-FLIP-DM is low doses of Gemcitabine, Fluorouracil \[5FU\], Leucovorin, Irinotecan, Oxaliplatin, Docetaxel and Mitomycin C

Also known as: Low dose Gemcitabine, Low dose Fluorouracil or 5FU, Leucovorin, Low dose Irinotecan, Low dose Oxaliplatin, Low dose Docetaxel, Low dose Mitomycin C

G-FLIP+VitaminC, then G-FLIP-DM+VitaminC; G-FLIP, then G-FLIP-DM

Vitamin C DIETARY_SUPPLEMENT

High dose of Vitamin C, used in combination with G-FLIP and then G-FLIP-DM

Also known as: Ascorbic Acid

G-FLIP+VitaminC, then G-FLIP-DM+VitaminC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically and cytologically confirmed metastatic (Stage IV), locally advanced unresectable (stage III), or locally recurrent pancreatic adenocarcinoma, with or without prior chemotherapy for their cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status being 0-2.
• Expected survival \>3 months.
• Patients 18 years of age and older of both genders.
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 2 weeks prior to treatment initiation.
• Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.
• At least 2 weeks must have elapsed from any prior surgery or hormonal therapy.
• Laboratory values ≤2 weeks must be:
• Adequate hematologic
• Adequate hepatic function
• Adequate renal function
• No evidence of active infection and no serious infections within the past month.
• Mentally competent, able to understand and willing to sign the informed consent form.

You may not qualify if:

• Patients under the age of 18.
• Locally advanced resectable disease from pancreatic cancer
• Previous radiotherapy for cerebral metastases, central nervous system (CNS) or epidural tumor.
• Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any non-cancer indication within the past 4 weeks.
• Patients with any active uncontrolled bleeding, or a bleeding diathesis.
• Pregnant women, or women of child-bearing potential not using reliable means of contraception.
• Lactating females.
• Fertile men unwilling to practice contraceptive methods during the study period.
• Life expectancy less than 3 months.
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
• Unwilling or unable to follow protocol requirements.
• Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, or symptomatic congestive heart failure.
• Patients with a history of myocardial infarction that is \< 3 months prior to registration.
• Patients with any amount of clinically significant pericardial effusion.
• Evidence of active serious infection.

Sponsors & Collaborators

• Bruckner Oncology: lead
• Hirschfeld Oncology: collaborator

Study Sites (1)

Bruckner Oncology

The Bronx, New York, 10469, United States

Location

Related Publications (5)

• Bruckner H, Hirschfeld A, Buddaraju S, Stega J, Jahan M, Schwartz ME. Multidisciplinary effect of adding docetaxel and mitomycin-C to low-dose multidrug therapy for cholangiocarcinoma. J Clin Oncol 29: 2011 (suppl; abstr e14546)

  BACKGROUND

• Bruckner HW, Myo M, Zaw K, Filipova O, Heidarian S, Rafiq N, Julliard K. Multi-drug chemotherapy for pancreatic cancer. Journal of Clinical Oncology 2005, 23 (16S. June 1 Supplement):4267 (abstract).

  BACKGROUND

• Bruckner H, Simon K, Hrehorovich V. Low-dose sequential multi-drug regimens for advanced pancreatic cancer. Journal of Clinical Oncology, 2008, 26 (15S, May 20 Supplement) 15568 (Abstract)

  BACKGROUND

• Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794. doi: 10.1371/journal.pone.0029794. Epub 2012 Jan 17.

  PMID: 22272248 BACKGROUND

• Goel A, Grossbard ML, Malamud S, Homel P, Dietrich M, Rodriguez T, Mirzoyev T, Kozuch P. Pooled efficacy analysis from a phase I-II study of biweekly irinotecan in combination with gemcitabine, 5-fluorouracil, leucovorin and cisplatin in patients with metastatic pancreatic cancer. Anticancer Drugs. 2007 Mar;18(3):263-71. doi: 10.1097/CAD.0b013e3280121334.

  PMID: 17264757 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Fluorouracil; Leucovorin; Irinotecan; Oxaliplatin; Gemcitabine; Docetaxel; Mitomycin; Ascorbic Acid

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Mitomycins; Indolequinones; Quinones; Azirines; Indoles; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Dr. Azriel Hirschfeld
• Organization: Hirschfeld Oncology

ah@honcology.com

718-732-4050

Study Officials

• Azriel Hirschfeld, MD

  Bruckner Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2013
• First Posted: July 23, 2013
• Study Start: August 13, 2014
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: December 11, 2024
• Results First Posted: August 14, 2024

Record last verified: 2020-01

Locations

US (1)