Phase II Trial Evaluating OS With Therasphere® + 2nd-Line FOLFOX in Pancreatic Liver Mets

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
BTG International Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01581307
First received: April 18, 2012
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the safety and impact on survival with treatment with 90-Y glass microspheres in conjunction with leucovorin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) as second-line treatment with in patients gemcitabine-refractory metastatic pancreatic cancer with predominantly liver metastases.


Condition Intervention Phase
Liver Cancer
Pancreatic Cancer
Drug: FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin)
Device: TheraSpheres
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial Evaluating Overall Survival With Therasphere® In Conjunction With 2nd-Line FOLFOX In Patients With Gemcitabine-Refractory Pancreatic Carcinoma With Liver Metastases

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Overall Survival (OS) [ Time Frame: Average of 9 months ] [ Designated as safety issue: No ]
    OS, defined as the time from study enrollment to death from any cause, will be analyzed and summarized with the survival probabilities over time using Kaplan-Meier method. Confidence intervals for the median OS rates at different time points will be constructed when appropriate.


Secondary Outcome Measures:
  • Number of Participants With Progression Free Survival (PFS) [ Time Frame: Average of 9 months ] [ Designated as safety issue: No ]
    PFS defined as the time from study enrollment to progression in the liver by modified Response Evaluation Criteria in Solid Tumors (RECIST) or death, whichever occurs first will be analyzed and summarized with the survival probabilities over time using Kaplan-Meier method. Confidence intervals for the median PFS rates at different time points will be constructed when appropriate.

  • Overall Response Rate (ORR) [ Time Frame: Average of 9 months ] [ Designated as safety issue: No ]
    The overall response: ORR = complete response (CR) + partial response (PR). Rate will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by groups.

  • Number of Participants With Adverse events [ Time Frame: Average of 9 months ] [ Designated as safety issue: Yes ]
    Common Toxicity Criteria for Adverse Effects (CTCAE) v4 toxicity


Estimated Enrollment: 58
Study Start Date: April 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2nd Line Chemotherapy With Radiotherapy

Administration of 2nd line chemotherapy will consist of a modified FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin) will take place at least 2 weeks after the completion of first‐line chemotherapy. Generally, second‐line chemotherapy is given every two weeks for 6‐10 cycles.

The goal of treatment with TheraSpheres is to allow a large dose of radiation to be delivered directly to the tumor(s) with less risk of toxic effects from radiation to other parts of the body or to healthy liver tissue.

Drug: FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin)
The usual treatment if gemcitabine chemotherapy has failed is chemotherapy with a drug combination called FOLFOX (folinic acid, 5-FU and oxaliplatin) given through a vein every 2 weeks for 6-10 cycles. Participants will receive this treatment.
Other Names:
  • Leucovorin
  • LV
  • FOL
  • OX
  • 5-Fluorouracil (5-FU)
  • FOLFOX
  • ELOXATIN
Device: TheraSpheres
TheraSpheres are a medical device containing yttrium-90 (Y-90), a radioactive material that has been used previously in the treatment of liver tumors. Y-90 is incorporated into very tiny glass beads called microspheres and is injected into the liver through the blood vessels supplying the liver. TheraSpheres have restricted approval from the United States Food and Drug Administration (FDA) for the treatment of hepatocellular liver cancer; but has not yet been approved for the treatment of pancreatic cancer that has spread to the liver.
Other Names:
  • radiotherapy
  • radioembolization

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have metastatic pancreatic cancer with predominantly liver metastatic disease (> 50%), as determined by the principal investigator (PI0 and referring medical oncologist that have progressed on gemcitabine-based chemotherapy.
  • Patients can have solitary, multifocal unilobar, or bilobar disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
  • No prior radiation or embolization of the liver
  • Childs-Pugh score ≤ 7
  • Lung shunting that predicts lung dose to be ≤ 30 Gy in a single treatment
  • The effects of TheraSpheres on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radioactive spheres are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document
  • Adequate baseline hematopoietic function:

    • total white blood cell count equal to or greater than 3,000/mm^3
    • absolute granulocyte count greater than 1,500/mm^3
    • platelet count equal to or greater than 50,000/mm^3
    • Hemoglobin > 8.0

Exclusion Criteria:

  • Patients currently receiving any other investigational agents
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because TheraSpheres are radioactive and radiation is a known agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TheraSpheres, breastfeeding should be discontinued if the mother is treated with TheraSpheres.
  • Initiation of second-line chemotherapy not consisting of FOLFOX
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. In addition, antiretrovirals are known radiation sensitizers and could dramatically increase the risk of fulminant hepatic failure. Therefore, human immunodeficiency virus(HIV)-positive patients are excluded from the study because of possible lethal side effects.
  • Bulk disease (tumor volume > 70% of the target liver volume)
  • Aspartic transaminase (AST) or alanine transaminase (ALT) > 5 times upper limit of normal (ULN)
  • Bilirubin > 2 mg/dL
  • Child-Pugh score > 7
  • Tumor volume > 50% of liver combined with an albumin < 3 g/dL
  • Complete occlusion of main portal vein causing portal hypertension
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01581307

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
BTG International Inc.
Investigators
Principal Investigator: Ravi Shridhar, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01581307     History of Changes
Other Study ID Numbers: MCC-16764
Study First Received: April 18, 2012
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
liver
pancreas
chemotherapy
radiotherapy

Additional relevant MeSH terms:
Pancreatic Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Liver Diseases
Levoleucovorin
Folic Acid
Fluorouracil
Oxaliplatin
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 30, 2014