Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer

NCT01821729 | Unknown Phase 2 Results DMC

• 1 other identifier: 13-051
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II clinical trial, which tests the safety and effectiveness of an investigational combination of drugs to learn whether the combination of drugs works in treating a specific cancer. "Investigational" means that the combination of drugs is being studied. It also means that the FDA has not yet approved it for your type of cancer. Proton beam radiation therapy is an FDA approved radiation delivery system. Conventional radiation therapy uses photons to treat cancer before patients undergo surgery to remove the tumor. In this study we are using radiation with protons, which spares surrounding tissue and organs from radiation. Proton radiation delivers radiation to the area requiring radiation with no dose beyond the treatment area. This may reduce side effects that patients would normally experience with conventional radiation therapy. Researchers in the laboratory have discovered pathways inside cancer cells which contribute to the growth and survival of tumors. The FOLFIRINOX chemotherapy regimen is a combination of the drugs 5-fluorouracil, leucovorin and oxaliplatin. These chemotherapy drugs, along with the chemotherapy drug capecitabine, work by blocking these pathways and thereby preventing tumor growth. Capecitabine is FDA approved to be used alone or with other drugs to treat other types of advanced cancer, but not pancreatic cancer. In past research studies, FOLFIRINOX followed by radiation therapy with capecitabine has been identified as the most effective and active chemotherapy for patients with cancer that is spreading, and this is why we are using it to treat your type of cancer. Losartan is classified as an angiotensin-receptor blocker (ARB), and is FDA approved for use in people with high blood pressure. Recent studies in people with different types of cancer, including pancreatic cancer, have shown that combining chemotherapy drugs with an ARB can help reduce/stop tumor growth more effectively than chemotherapy alone. Losartan has been used in previous research studies, and information from those research studies suggests that this drug in combination with FOLFIRINOX and capecitabine may be better at treating your type of cancer. In this research study, we seek to determine whether combining FOLFIRINOX with Losartan before proton radiation therapy will be more efficient at controlling the growth of or shrinking your tumor than just FOLFIRINOX alone.

Conditions

Pancreatic Cancer

Keywords

Locally Advanced

Outcome Measures

Primary Outcomes (1)

• Number of Participants With R0 Resection

  The number of participants that received treatment with proton radiation along with FOLFIRINOX-Losartan and then subsequently underwent attempted surgery and achieved R0 resection. R0 resection means that no cancer cells were seen microscopically at the resection margin.

  At the time of surgery (approximately 4 months after the start of treatment)

Secondary Outcomes (10)

• Progression-Free Survival

  From the start of treatment until death or progression, median duration of 17.5 months

• Overall Survival for FOLFIRINOX + Proton Beam Radiation

  2 years

• Overall Survival for FOLFIRINOX Without Proton Radiation

  2 years

• Determine Toxicity FOLFIRINOX-Losartan

  2 years

• Determine Toxicity of FOLFIRINOX-Losartan and Proton Beam Radiation

  2 years

Study Arms (1)

Experimental Arm

EXPERIMENTAL

FOLFIRINOX, Losartan, Proton Beam Radiation Therapy

Drug: FOLFIRINOX; Drug: Losartan; Radiation: Proton Beam Radiation

Interventions

FOLFIRINOX DRUG

Oxaliplatin via IV on Day 1 over 2 hours; Irinotecan via IV on Day 1 over 90 minutes, 5FU via IV on Day 1 over 2-4 minutes

Also known as: 5-Fluorouracil, 5FU, Leucovorin, Oxaliplatin

Experimental Arm

Losartan DRUG

Taken orally every day during Phase I for all 8 cycles

Experimental Arm

Proton Beam Radiation RADIATION

30-45 minutes per day, daily Monday-Friday

Experimental Arm

Eligibility Criteria

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

You may qualify if:

• Cytologic or histologic proof pancreatic ductal carcinoma
• Locally advanced, unresectable disease
• Life expectancy of at least 3 months

You may not qualify if:

• Evidence of metastatic disease
• Pregnant or breastfeeding
• Serious concomitant systemic disorders incompatible with the study
• Already treated on ACE or ARB therapy for hypertension or renal protection at the time of enrollment
• Baseline hypotension
• Prior chemotherapy, radiation therapy, or biologic therapy for treatment of pancreatic tumor
• Treatment for other invasive carcinomas within the last 5 years who are greater than 5% risk of recurrence at the time of eligibility screening (carcinoma in-situ and basal cell carcinoma/squamous cell carcinoma of the skin are allowed)
• Other serious uncontrolled medical conditions
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• Known, existing coagulopathy
• Prior systemic fluoropyrimidine therapy
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance or oral drug intake
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment
• Taking cimetidine

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• Wang H, Yuan S, Wang H. Current Status of Research on Losartan in Tumour Therapy. J Cell Mol Med. 2026 Jan;30(1):e70985. doi: 10.1111/jcmm.70985.

  PMID: 41486497 DERIVED

• Murphy JE, Wo JY, Ryan DP, Clark JW, Jiang W, Yeap BY, Drapek LC, Ly L, Baglini CV, Blaszkowsky LS, Ferrone CR, Parikh AR, Weekes CD, Nipp RD, Kwak EL, Allen JN, Corcoran RB, Ting DT, Faris JE, Zhu AX, Goyal L, Berger DL, Qadan M, Lillemoe KD, Talele N, Jain RK, DeLaney TF, Duda DG, Boucher Y, Fernandez-Del Castillo C, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):1020-1027. doi: 10.1001/jamaoncol.2019.0892.

  PMID: 31145418 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Fluorouracil; Leucovorin; Oxaliplatin; Losartan; Proton Therapy

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; Coordination Complexes; Organic Chemicals; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Imidazoles; Azoles; Tetrazoles; Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Theodore Hong
• Organization: Massachusetts General Hospital

TSHONG1@mgh.harvard.edu

617-726-6050

Study Officials

• Theodore Hong, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 27, 2013
• First Posted: April 1, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2018
• Study Completion: September 1, 2021
• Last Updated: September 25, 2020
• Results First Posted: September 17, 2019

Record last verified: 2020-09

Locations

US (1)