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Trial record 34 of 38 for:    MM-398

Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy

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ClinicalTrials.gov Identifier: NCT03883919
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : July 17, 2019
Sponsor:
Collaborator:
Ipsen
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
Given the efficacy of nanoliposomal irinotecan as a second-line regimen in pancreatic ductal adenocarcinoma (PDAC), together with the favorable toxicity profile of paricalcitol and its interplay with irinotecan metabolism, the investigators propose a second-line pilot study in advanced PDAC that will enroll patients who have progressed on a gemcitabine-based regimen.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Pancreas Cancer Cancer of the Pancreas Drug: 5-FU Drug: Leucovorin Drug: Liposomal Irinotecan Drug: Paricalcitol Procedure: Serum and plasma blood samples Procedure: Tumor biopsy Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy
Actual Study Start Date : July 11, 2019
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Group 1: Paricalcitol 75 mcg Days 1 and 8
  • 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
  • Paricalcitol 75 mcg on Days 1 and 8
  • treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
Drug: 5-FU
-Standard of care drug
Other Names:
  • Fluorouracil
  • Adrucil

Drug: Leucovorin
-Standard of care drug
Other Names:
  • Wellcovorin
  • Folinic acid

Drug: Liposomal Irinotecan
-Standard of care drug
Other Names:
  • nal-IRI
  • Onivyde

Drug: Paricalcitol
-Investigational drug
Other Names:
  • Zemplar
  • Vitamin D

Procedure: Serum and plasma blood samples
-baseline, day 1 of each cycle beginning with cycle 2

Procedure: Tumor biopsy
  • Fresh core tumor biopsies will be obtained from the primary pancreatic site or metastatic site prior to cycle 1
  • After Cycle 3 of treatment, all patients will be required to undergo biopsy of a metastatic site or the primary pancreatic tumor, if biopsy of a metastatic site is not able to be safely obtained.

Experimental: Group 2: Paricalcitol 7 mcg/kg Days 1 and 8
  • 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle.
  • Paricalcitol 7 mcg/kg on Days 1 and 8
  • treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
Drug: 5-FU
-Standard of care drug
Other Names:
  • Fluorouracil
  • Adrucil

Drug: Leucovorin
-Standard of care drug
Other Names:
  • Wellcovorin
  • Folinic acid

Drug: Liposomal Irinotecan
-Standard of care drug
Other Names:
  • nal-IRI
  • Onivyde

Drug: Paricalcitol
-Investigational drug
Other Names:
  • Zemplar
  • Vitamin D

Procedure: Serum and plasma blood samples
-baseline, day 1 of each cycle beginning with cycle 2

Procedure: Tumor biopsy
  • Fresh core tumor biopsies will be obtained from the primary pancreatic site or metastatic site prior to cycle 1
  • After Cycle 3 of treatment, all patients will be required to undergo biopsy of a metastatic site or the primary pancreatic tumor, if biopsy of a metastatic site is not able to be safely obtained.




Primary Outcome Measures :
  1. Tolerability between two different dose levels of paricalcitol added to the combo regimen of liposomal irinotecan plus 5-FU / LV as measured by the occurrence of grade 3 and 4 toxicities [ Time Frame: Through 30 days after completion of treatment (estimated to be 28 weeks) ]
    -Toxicity will be graded using CTCAE version 5.0


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Through completion of cycle 9 (estimated to be 18 weeks) ]
    • The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and disappearance of all non-target lesions and normalization of tumor marker level.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  2. Progression-free survival (PFS) [ Time Frame: Through completion of follow-up (estimated to be 72 weeks) ]
    • PFS: PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

  3. Overall survival (OS) [ Time Frame: Through completion of follow-up (estimated to be 72 weeks) ]
    -Overall survival (OS) is defined as the date from treatment to death or last follow-up.

  4. CA19-9 biochemical response rate [ Time Frame: Through beginning of cycle 10 (estimated to be 18 weeks) ]
    -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9.

  5. Duration of overall response [ Time Frame: Through completion of cycle 9 (estimated to be 18 weeks) ]
    - The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

  6. Duration of complete response [ Time Frame: Through completion of cycle 9 (estimated to be 18 weeks) ]
    • The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and disappearance of all non-target lesions and normalization of tumor marker level.

  7. Duration of stable disease [ Time Frame: Through completion of cycle 9 (estimated to be 18 weeks) ]
    • Duration of stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed pancreatic adenocarcinoma.
  • Must have progressed on or become intolerant to gemcitabine-containing therapy in the advanced setting (not resectable).
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • At least 18 years of age.
  • Life expectancy > 3 months.
  • ECOG performance status ≤ 1
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL
    • Hemoglobin ≥ 9 g/dL
    • Total bilirubin ≤ 1.5 x ULN
    • Serum albumin > 3g/dL
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless there are liver metastases, in which case AST and ALT ≤ 5.0 x IULN
    • Creatinine ≤ 1.5 x IULN OR GFR > 50 mL/min
    • Corrected serum calcium < 10.3 mg/dL
    • Serum phosphorus ≤ 4.5 mg/dL
  • Patients will require a 2-week washout period from previous gemcitabine-based systemic therapy prior to the first planned dose of study treatment.
  • Prior treatment-related toxicity must recover to grade 1 or less prior to the first planned dose of study treatment.
  • Women of childbearing 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 must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Patients with active renal, ureteral, or bladder stones on the screening imaging.
  • Current use of or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment.
  • A history of other malignancy within 2 years previous, with the exception of those basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix.
  • Currently receiving any other investigational agents.
  • Patients who received FOLFIRINOX or FOLFIRI in the neoadjuvant or adjuvant setting who experienced disease recurrence within 6 months will be excluded (patients who received 5-FU or capecitabine as a radiosensitizer are permitted to enroll.)
  • Patients with known active/ progressive brain metastases or leptomeningeal involvement will be excluded due to their poor prognosis. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry, are eligible.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, liposomal irinotecan, 5-FU, LV, or other agents used in the study.
  • Clinical significant ascites that requires therapeutic paracentesis or significant pleural effusion that requires therapeutic thoracentesis.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
  • Known HIV-positivity not on anti-retroviral therapy, or with CD4+ T cell count < 200/ul (patients with known HIV currently on anti-retroviral therapy with CD4+ T cell count > 200/ul will be included).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03883919


Contacts
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Contact: Andrea Wang-Gillam, M.D., Ph.D. 314-362-5740 awang-gillam@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Andrea Wang-Gillam, M.D., Ph.D.    314-362-5740    awang-gillam@wustl.edu   
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D.         
Sub-Investigator: Manik Amin, M.D.         
Sub-Investigator: Patrick Grierson, M.D., Ph.D.         
Sub-Investigator: Kian-Huat Lim, M.D., Ph.D.         
Sub-Investigator: Haeseong Park, M.D.         
Sub-Investigator: Katrina Pedersen, M.D., M.S.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Benjamin R Tan, M.D.         
Sub-Investigator: Nikolaos Trikalinos, M.D.         
Sub-Investigator: Esther Lu, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Ipsen
Investigators
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Principal Investigator: Andrea Wang-Gillam, M.D, Ph.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03883919     History of Changes
Other Study ID Numbers: 201905201
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Plan for sharing IPD to be determined.
Time Frame: Time frame for accessing IPD to be determined.
Access Criteria: Access criteria for sharing IPD to be determined.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Irinotecan
Ergocalciferols
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Calcium-Regulating Hormones and Agents
Vitamins
Micronutrients
Nutrients
Growth Substances
Bone Density Conservation Agents