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Acinar Cell Adenocarcinoma of the PancreasPhase 1NCT01643499

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

A Phase 1 study testing oxaliplatin, irinotecan hydrochloride and leucovorin calcium in people with Acinar Cell Adenocarcinoma of the Pancreas and Adenocarcinoma of the Gallbladder, run by University of Chicago at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is being done to determine the dose of a chemotherapy drug (irinotecan [irinotecan hydrochloride]) that can be tolerated as part of a combination of drugs. There is a combination of chemotherapy drugs often used to treat gastrointestinal cancer, which consists of 5-FU (fluorouracil), leucovorin (leucovorin… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
oxaliplatin, irinotecan hydrochloride and leucovorin calcium
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
2 sitesUnited States
Study dates
26 Mar 2012to Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, colorectal adenocarcinoma, gastric adenocarcinoma, cholangiocarcinoma, gall bladder adenocarcinoma, ampullary carcinoma, adenocarcinoma of unclear primary (with a gastrointestinal primary suspected), or other primary gastrointestinal malignancy for which the treating physician feels that mFOLFIRINOX is a reasonable therapeutic option.
  • Amendment (January 2014): only subjects with the following histologies will be eligible
  • Cohort # 1 (pancreatic cohort): locally advanced or metastatic pancreatic adenocarcinoma (19 subjects evaluable for the primary endpoint after the amendment)
  • Cohort #2 (biliary tract cohort): locally advanced or metastatic cholangiocarcinoma, gall bladder adenocarcinoma, or ampullary carcinoma (19 subjects evaluable for the primary endpoint after the amendment). Patients with adenocarcinoma of unclear primary that are most likely of biliary tract origin (in the opinion of the treating physician) will also be allowed on this cohort.
  • Patients with a history of obstructive jaundice due to the primary tumor must have a metal biliary stent in place,
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1,
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  • Life expectancy > 3 months,
  • Absolute neutrophil count (ANC) >= l500/ul,
  • Hemoglobin >= 9g/dL,
  • Platelets >= 100,000/ ul,
  • Total bilirubin < 1.5 x upper limit of normal,
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver metastases,
  • Creatinine =< 1.5 x upper limit of normal,
  • Measurable or non-measurable disease will be allowed,
  • 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, up until 30 days after final study treatment; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately,
  • Patients taking substrates, inhibitors, or inducers of Cytochrome P450 3A4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
  • Signed informed consent.

Who cannot join

  • Prior chemotherapy or radiation therapy for any cancer,
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis),
  • Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v. 4.0); pancreatic cancer patients with clinical evidence of pancreatic insufficiency must be taking pancreatic enzyme replacement,
  • Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0,
  • Documented brain metastases,
  • Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment,
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  • Active uncontrolled bleeding,
  • Pregnancy or breastfeeding,
  • Major surgery within 4 weeks,
  • Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%,
  • Patients with any polymorphism in UGT1A1 other than *1 or *28.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637-1470

  • Evanston CCOP-NorthShore University HealthSystem

    Evanston, Illinois, 60201

Other trials in United States

About this study

Official title: A Genotype-guided Dosing Study of mFOLFIRINOX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies

This study is being done to determine the dose of a chemotherapy drug (irinotecan [irinotecan hydrochloride]) that can be tolerated as part of a combination of drugs. There is a combination of chemotherapy drugs often used to treat gastrointestinal cancer, which consists of 5-FU (fluorouracil), leucovorin (leucovorin calcium), irinotecan and oxaliplatin and is known as "FOLFIRINOX". FOLFIRINOX is a current drug therapy combination (or regimen) used for people with advanced pancreatic cancer, although this combination is not Food and Drug Administration (FDA) approved for this indication. FOLFIRINOX was recently shown in a separate clinical trial to increase survival compared to another commonly used drug in pancreatic cancer called gemcitabine. FOLFIRINOX is also a reasonable regimen for those with other advanced cancers of the gastrointestinal tract, including colon cancer, rectal cancer, esophagus cancer, stomach cancer, gall bladder cancer, bile duct cancer, ampullary cancer, and cancers with an unknown primary location. The best dose of irinotecan to use in FOLFIRINOX is not known. This study will analyze one gene (uridine 5'-diphospho [UDP] glucuronosyltransferase 1 family, polypeptide A1 [UGT1A1] gene) of subjects for the presence of an alteration in that gene, which may affect how the body handles irinotecan. Genes help determine some of the investigators individual characteristics, such as eye color, height and skin tone. Genes may also determine why people get certain diseases and how medicines may affect them. The result of the genetic analysis will divide subjects into one of three groups: A, B, or C. Group A (approximately 45% of subjects) will receive the standard dose of irinotecan. Group B (approximately 45% of subjects) will receive a lower dose of irinotecan. Group C (approximately 10% of subjects) will receive an even lower dose of irinotecan

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the dose-limiting toxicity (DLT) rate in cycle #1 in each of two UGT1A1 genotype groups (*1*1, *1*28) using genotype-guided dosing of irinotecan as part of the modified (m) FOLFIRINOX regimen.

SECONDARY OBJECTIVES:

  1. To determine the cumulative dose intensity of irinotecan achieved in each genotype group.

II. To determine the response rates by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) for each different disease (pancreatic cancer, biliary cancers, gastric cancer, colorectal cancer, adenocarcinoma of unknown primary) treated in the study.

OUTLINE:

Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 1.5 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Being tested
oxaliplatin, irinotecan hydrochloride, leucovorin calcium, fluorouracil, laboratory biomarker analysis
Medical subject headings
Neoplasms, Unknown Primary, Bile Duct Neoplasms, Pancreatic Neoplasms, Colonic Neoplasms, Gallbladder Neoplasms, Stomach Neoplasms, Rectal Neoplasms

What participants receive

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

  • oxaliplatinDrug

    Also called 1-OHP, Dacotin, Dacplat, Eloxatin

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01643499
Study groupRoleWhat they receive
Treatment (mFOLFIRINOX)ExperimentalPatients receive oxaliplatin IV over 2 hours on, irinotecan hydrochloride IV over 1.5 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: oxaliplatin; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: fluorouracil; Other: laboratory biomarker analysis

What is being measured

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

  1. DLT rate in course 1 for each of the two most common genotype groups (*1*1 and *1*28)

    To show that the DLT rate is less than 33% with at least 70-80% confidence, which is comparable to the standard 3+3 phase I design with 0 out of 3 or 1 out of 6 patients experiencing a DLT.

    Measured: 4 weeks

Secondary outcomes (2)

  1. Response rates (by RECIST 1.1) for patients with each different type of gastrointestinal malignancy

    Measured: Up to 1 year

  2. Cumulative dose intensity of irinotecan hydrochloride

    Measured: Up to 1 year

Timeline

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

  1. First posted18 Jul 2012 (estimated)
  2. Study start26 Mar 2012
  3. Primary completion28 Aug 2016
  4. Study completionJul 2019

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01643499
Sponsor's protocol ID
12-0033
Other IDs
NCI-2012-00585
Status last verified
May 2020
First submitted
16 Jul 2012
Last updated
8 May 2020
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing oxaliplatin, irinotecan hydrochloride and leucovorin calcium in people with Acinar Cell Adenocarcinoma of the Pancreas and Adenocarcinoma of the Gallbladder, run by University of Chicago at 2 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 17 inclusion and 11 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: finished, as of the sponsor's last update on 8 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

DLT rate in course 1 for each of the two most common genotype groups (*1*1 and *1*28) (time frame: 4 weeks). 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 NCT01643499.

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 8 May 2020.

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