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Metastatic Biliary Tract CarcinomaPhase 1/2NCT03337087

Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer

A Phase 1/2 study testing Fluorouracil, Irinotecan Sucrosofate and Laboratory Biomarker Analysis in people with Metastatic Biliary Tract Carcinoma and Metastatic Colorectal Carcinoma, run by Academic and Community Cancer Research United at 3 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of liposomal irinotecan and rucaparib when given together with fluorouracil and leucovorin calcium and to see how well they work in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer that has spread to other places in the body… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fluorouracil, Irinotecan Sucrosofate and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
3 sitesUnited States
Study dates
2 Nov 2018to 9 Aug 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phase I only: Histologic confirmation of pancreatic, colorectal, gastroesophageal or biliary adenocarcinoma, as follows:
  • Patients with metastatic disease from pancreatic cancer who received no more than 2 lines of prior therapy in the metastatic setting
  • Patients with metastatic disease from colorectal cancer who received no more than 3 lines of prior therapy in the metastatic setting
  • Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting
  • Patients with metastatic disease from biliary tract cancer who received no more than 1 line of prior therapy in the metastatic setting
  • NOTE: No prior exposure to irinotecan in the metastatic setting will be allowed except in the phase I dose escalation portion and in colon cancer patients only; in pancreas cancer, exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
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  • Phase Ib only: Patients with metastatic adenocarcinoma of the pancreas who have who received no more than 1 line of prior therapy in the metastatic setting
  • NOTE: Exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
  • Phase II only: Patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD) or BRCA1 or BRCA2 or PALB2 mutation, or HRD (non-BRCA, non-PALB) who have not received any systemic therapy in the metastatic setting
  • NOTE: Exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 21 days prior to registration)
  • Platelet count >= 100,000/mm^3 (obtained =< 21 days prior to registration)
  • Hemoglobin > 9.0 g/dL (obtained =< 21 days prior to registration)
  • Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 21 days prior to registration)
  • Aspartate transaminase (AST) =< 3 x ULN, =< 5.0 x ULN for patients with metastatic disease to the liver (obtained =< 21 days prior to registration)
  • Aminotransferase (ALT) =< 3.0 x ULN, =< 5.0 x ULN for patients with metastatic disease to the liver (obtained =< 21 days prior to registration)
  • Creatinine =< 1.0 mg/dL or creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 21 days prior to registration)
  • Negative serum or urine pregnancy test done =< 7 days prior to registration and repeated prior to dosing on day 1 of each cycle, for individuals of childbearing potential only; NOTE: Individuals are considered to be of childbearing potential unless one of the following applies:
  • Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause; a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state: or
  • Considered to be permanently sterile; permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Willing to provide tissue and blood samples for mandatory correlative research purposes
  • Individuals of reproductive potential and their partners willing to practice total abstinence or use a highly effective method of contraception (failure rate < 1% per year) during treatment and for 6 months following the last dose of rucaparib; the following are allowable only:
  • Ongoing use of progesterone-only injectable or implantable contraceptives (eg, Depo Provera, Implanon, Nexplanon)
  • Placement of an intrauterine device or intrauterine system
  • Bilateral tubal occlusion
  • Sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate
  • True, complete (as opposed to periodic) abstinence
  • Patients must discontinue prior chemotherapy >= 28 days before registration

Who cannot join

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant individuals
  • Nursing individuals
  • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
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  • 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
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Previous or concurrent cancer that is distinct in primary site or histology from cancer of primary site =< 3 years prior to registration EXCEPT for curatively treated cervical cancer in situ, melanoma in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]; Note: All cancer treatments for those distinct in a primary site other than cancer of origin must be completed >= 3 years prior to registration
  • Received any prior poly ADP-ribose polymerase inhibitor (PARPi) treatment. Patients who received prior PARPi treatment in the adjuvant setting with the last dose received more than 12 months prior to registration are allowed to enroll.
  • Corrected QT interval (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard
  • Inability to swallow

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase I Study of Irinotecan Liposome (Nal-IRI), Fluorouracil and Rucaparib in the Treatment of Select Gastrointestinal Metastatic Malignancies Followed by a Phase Ib of First and Second Line Treatment of Both Unselected and Selected (for BRCA 1/2 and PALB2 Mutations) Patients With Metastatic Adenocarcinoma of the Pancreas Then Followed by a Phase II Study of First Line Treatment of Selected Patients With Metastatic Adenocarcinoma of the Pancreas With Genomic Markers (Signature) of Homologous Recombination Deficiency (HRD)

This phase I/II trial studies the side effects and best dose of liposomal irinotecan and rucaparib when given together with fluorouracil and leucovorin calcium and to see how well they work in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as liposomal irinotecan, fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as rucaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving liposomal irinotecan and rucaparib together with fluorouracil and leucovorin calcium may work better in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To establish the recommended dose level for the phase Ib and phase II trial of liposomal irinotecan (nal-IRI) and fluorouracil (5-FU) with rucaparib (MFR) in patients with metastatic disease from pancreatic cancer (up to 2 lines of prior therapy), colorectal cancer (up to 3 lines of prior therapy), gastroesophageal cancer (up to 1 line of prior therapy) and biliary tract cancer (with 1 line of prior therapy allowed). (Phase I) II. To assess, in a preliminary fashion, antitumor efficacy, in terms of disease control rate and further tolerability, of the recommended dose level of combination of nal-IRI and 5-FU with rucaparib in patients with metastatic disease from pancreatic cancer (=< 1 line of prior therapy in the metastatic setting). (Phase Ib) III. To estimate the proportion of evaluable patients who reach complete response (CR)/partial response (PR) =< 32 weeks after registration among patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1, BRCA2, and PALB2 mutation, treated with the combination of nal-IRI and 5FU with rucaparib (MFR). (Phase II)

SECONDARY OBJECTIVES:

  1. To estimate the progression-free survival (PFS) and overall survival (OS) for patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1, BRCA2, and PALB2 mutation, treated with the combination of nal-IRI and 5-FU with rucaparib (MFR). (Phase II) II. To assess the toxicity of the combination of nal-IRI and 5-FU with rucaparib in patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1/2 and PALB2 mutations. (Phase II)

EXPLORATORY OBJECTIVES:

  1. To evaluate the role of genomic markers (signature) of HRD, mutation other than BRCA1, BRCA2, and PALB2 as predictive biomarkers of response to MFR.

II. To evaluate BRCA1, BRCA2, and PALB2 mutations as predictive biomarker of response to MFR.

OUTLINE: This is phase I, dose-escalation study of liposomal irinotecan and rucaparib and followed by a phase II study.

PHASE Ia: Patients receive liposomal irinotecan intravenously (IV) over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib orally (PO) twice daily (BID) on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.

PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Being tested
Fluorouracil, Irinotecan Sucrosofate, Laboratory Biomarker Analysis, Leucovorin Calcium, Rucaparib
Medical subject headings
Colorectal Neoplasms, Gastrointestinal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Irinotecan SucrosofateDrug

    Also called Irinotecan Liposome, MM-398, nal-IRI, Nanoliposomal Irinotecan

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • RucaparibDrug

    Also called 6H-Pyrrolo(4,3,2-ef)(2)benzazepin-6-one, 8-Fluoro-1,3,4,5-tetrahydro-2-(4-((methylamino)methyl)phenyl)-, 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-1,3,4,5-tetrahydro-6H-azepino(5,4,3-cd)indol-6-one

    Given PO

Study groups in NCT03337087
Study groupRoleWhat they receive
Treatment (nal-IRI, leucovorin, fluorouracil, rucaparib)ExperimentalPHASE Ia: Patients receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Receives: Drug: Fluorouracil; Drug: Irinotecan Sucrosofate; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Rucaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose Limiting Toxicities (Phase I)

    Will be assessed to determine maximum tolerated dose (MTD) of the combination of liposomal irinotecan (nal-IRI) and fluorouracil (5FU) with rucaparib (MFR). MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.

    Measured: Up to 28 days from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2017
  2. Study start2 Nov 2018
  3. Primary completion31 Mar 2021
  4. Study completion9 Aug 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03337087
Sponsor's protocol ID
ACCRU-GI-1603
Other IDs
NCI-2017-01976, ACCRU-GI-1603, P30CA015083
Status last verified
May 2024
First submitted
6 Nov 2017
Last updated
17 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Fluorouracil, Irinotecan Sucrosofate and Laboratory Biomarker Analysis in people with Metastatic Biliary Tract Carcinoma and Metastatic Colorectal Carcinoma, run by Academic and Community Cancer Research United at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (Phase I) (time frame: Up to 28 days from start of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03337087.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.

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