An interventional study of PAGODA algorithm and Oxaliplatin in Ampulla of Vater Carcinoma, Appendix Carcinoma and Carcinoma of Unknown Primary With Gastrointestinal Profile, sponsored by Alliance for Clinical Trials in Oncology. Recruiting at 398 sites in 3 countries. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by Alliance for Clinical Trials in Oncology · Not applicable, Interventional, and Health services research
This clinical trial is being done to learn whether using the proactive, graduated dose modification algorithm for leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) (PAGODA) algorithm to guide chemotherapy dosing for the FOLFOX regimen works to reduce unplanned treatment delays for patients with digestive system cancers compared to usual care. During standard of care treatment, chemotherapy dose changes or treatment delays are typically determined by the treating physician based on factors such as a patient's height, weight, and blood test results obtained before each treatment cycle. If certain blood counts are too low, the next cycle of chemotherapy may be delayed or adjusted. The PAGODA algorithm is a step-by-step decision-making tool designed to help health care providers determine whether chemotherapy doses should be adjusted or delayed in patients with low neutrophil or platelet counts. Researchers will compare treatment delays, dose changes, and safety outcomes between patients managed using the PAGODA algorithm and patients receiving usual care.
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To compare the proportion of chemotherapy cycles with unplanned delays in patients receiving FOLFOX chemotherapy under standardized usual care (control) versus (vs) according to the PAGODA dose modification algorithm (intervention).
SECONDARY OBJECTIVES:
I. To compare the mean number of health care contact days (time toxicity) for patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms.
II. To compare the incidence moderate-to-severe neutropenia (absolute neutrophil count less than 1000/mm3 in patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms.
III. To compare the relative dose-intensity of bolus 5-FU, oxaliplatin, and infusional 5-FU in patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms, both overall and among the subgroup of participants treated with curative intent.
OUTLINE: This is an interventional study. Patients are randomized to 1 of 2 arms.
ARM A: Patients receive chemotherapy delays and dose modifications at the discretion of the treating clinician during cycles 2-7 of SOC FOLFOX chemotherapy on study.
ARM B: Patients receive chemotherapy delays and dose modifications based on PAGODA algorithm followed by treating clinician decision during cycles 2-7 of SOC FOLFOX chemotherapy on study.
After completion of study intervention, patients are followed up at 30 and 120 days and then every 12 months for 2 years following registration.
86 studies on the registry are indexed under Appendiceal Neoplasms; 25 are open to participants now.
This study's planned enrollment of 420 is above the median of 44 across 63 interventional studies indexed under Appendiceal Neoplasms.
Browse Appendiceal Neoplasms studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 509 studies on the registry; 28 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 28, 2026. See what changed
Inclusion Criteria:
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1)
Patients receiving concomitant therapy with irinotecan or docetaxel are not eligible
* NON-PATIENT (ONCOLOGY PHYSICIAN OR ONCOLOGY ADVANCED PRACTICE PROVIDER ELIGIBILITY:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive chemotherapy delays and dose modifications based on PAGODA algorithm followed by treating clinician decision during cycles 2-7 of SOC FOLFOX chemotherapy on study.
Other: PAGODA algorithm · Drug: Oxaliplatin · Drug: Folinic Acid · Drug: Fluorouracil
Patients receive chemotherapy delays and dose modifications at the discretion of the treating clinician during cycles 2-7 of SOC FOLFOX chemotherapy on study.
Drug: Oxaliplatin · Drug: Folinic Acid · Drug: Fluorouracil
use PAGODA algorithm to determine chemotherapy delays and dose modifications
Given IV
Given IV
Also known as: Leucovorin
Given IV
Also known as: 5-FU
Incidence of unplanned chemotherapy delays
Will employ a generalized linear mixed effects model with logit link function, with a random patient effect to account for clustering of cycles within patients. Will test if additional random effects are needed (e.g., provider or clinic level). Statistical significance will be assessed at the 5% level. Delays will be assessed over cycles 2 through 7, and a delay will be defined as an interval of \> 18 days since day 1 of the previous cycle. An unplanned delay will be defined as any delay that was not prospectively planned by day 3 of the previous cycle.
Time frame: From cycle 2 to 7 (Undelayed cycle length= 14 days)
Time toxicity
Will use health care contact days as a patient-level measure of time toxicity, as previously described by Gupta et al. Health care contact days will be assessed from electronic health record (EHR) data by recording the number of unique days on which the participant has any in-person contact with the health care system (e.g. for an office visit, chemotherapy treatment, laboratory study, emergency department visit, or other health care service). The mean number of health care contact days will be summarized and compared between the intervention arms using an independent two-sample t-test or Wilcoxon rank sum test. To adjust for multiple comparisons, statistical significance will be evaluated at the 1.25% alpha level.
Time frame: From registration to 120 days after registration.
Moderate-to-severe neutropenia
We will assess the patient-level occurrence of ANC less than 1000/mm3 through 30 days after day 1 of the last cycle of protocol treatment. The proportion of patients experiencing ANC less than 1000/mm3 will be summarized and compared between the intervention arms using a Chi-square test for independence or Fisher's Exact test.
Time frame: From the start of cycle 2 to 30 days after start of cycle 7 (undelayed cycle length= 14 days)
Chemotherapy relative dose intensity
Relative dose intensity (RDI) will be individually calculated for 5-FU bolus, oxaliplatin, and infusional 5-FU at the patient-level as the ratio of the delivered dose intensity (dose delivered divided by days elapsed between cycle 1 day 1 and cycle 6 day 14) and the standard dose intensity (standard dose divided by standard treatment interval). The RDI will be summarized and compared between the intervention arms using an independent two-sample t-test or Wilcoxon rank sum test. To adjust for multiple comparisons, statistical significance will be evaluated at the 1.25% alpha level. RDI will be calculated for the entire sample and within treatment intent. For subgroup analyses, statistical significance will be assessed at the 5% level and any positive findings will be considered hypothesis-generating.
Time frame: Time Frame: From the start of cycle 1 to day 14 of cycle 6 (undelayed cycle length= 14 days).
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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