A Phase 2/3 interventional study of Oxaliplatin and Duloxetine Hydrochloride in Stage II Colorectal Cancer AJCC v8 and Stage III Colorectal Cancer AJCC v8, sponsored by Alliance for Clinical Trials in Oncology. Active, not recruiting at 793 sites in 2 countries. Open to participants aged 25 Years and older. Per ClinicalTrials.gov, last updated 2026-01-26.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 2/3, Interventional, and Supportive care
This phase II/III trial studies the best dose of duloxetine and how well it works in preventing pain, tingling, and numbness (peripheral neuropathy) caused by treatment with oxaliplatin in patients with stage II-III colorectal cancer. Duloxetine increases the amount of certain chemicals in the brain that help relieve depression and pain. Giving duloxetine in patients undergoing treatment with oxaliplatin for colorectal cancer may help prevent peripheral neuropathy.
The primary and secondary objectives of the study:
PRIMARY OBJECTIVES:
I. To determine the dosage of duloxetine hydrochloride (duloxetine) (30 mg or 60 mg daily) that appears most promising in preventing oxaliplatin-induced peripheral neuropathy (OIPN). (Phase II)
II. To demonstrate that the most promising dosage of duloxetine identified in the Phase II component is more effective than placebo at preventing OIPN sensory symptoms. (Phase III)
III. To demonstrate that the most promising dosage of duloxetine identified in the Phase II component is more effective than placebo at preventing oxaliplatin-induced chronic neuropathic pain. (Phase III)
SECONDARY OBJECTIVES:
I. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. (Phase II)
II. To compare the serially measured OIPN total sensory neuropathy scores calculated from the six individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet), measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment between the most promising dosage of duloxetine identified in the Phase II component and placebo. (Phase III)
III. To compare the serially measured Brief Pain Inventory Short Form (BPI-SF) patient-reported on the average pain scores, measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment between the most promising dosage of duloxetine identified in the Phase II component and placebo.
IV. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using the CTCAE v 5.0. (Phase III)
OUTLINE:
PHASE II: Patients are randomized to 1 of 3 arms.
ARM I: Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD and placebo (1 placebo capsule) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.
ARM II: Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 60 mg (2 duloxetine capsules) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.
ARM III: Patients in Phase II receive placebo (1 placebo capsule) orally (PO) once daily (QD) during week 1, placebo (2 placebo capsules) PO QD weeks 2-16, followed by placebo (1 placebo capsule) PO QD during week 17 in the absence of unacceptable toxicity.
PHASE III: Patients are randomized to 1 of 2 arms.
ARM I: Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD in the absence of unacceptable toxicity.
ARM II: Patients in Phase III receive placebo PO QD in the absence of unacceptable toxicity.
NOTE: Patients in all arms receive standard of care oxaliplatin during weeks 1-12.
After completion of study, patients are followed up at 30 days and at 3, 6, 12, and 18 months after last oxaliplatin treatment.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's enrollment of 220 is above the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal 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.
Concomitant medications:
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.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
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.
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.
Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD and placebo (1 placebo capsule) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.
Drug: Oxaliplatin · Drug: Duloxetine Hydrochloride · Drug: Duloxetine · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Other: Placebo
Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 60 mg (2 duloxetine capsules) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.
Drug: Oxaliplatin · Drug: Duloxetine Hydrochloride · Drug: Duloxetine · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Patients in Phase II receive placebo (1 placebo capsule) orally (PO) once daily (QD) during week 1, placebo (2 placebo capsules) PO QD weeks 2-16, followed by placebo (1 placebo capsule) PO QD during week 17 in the absence of unacceptable toxicity.
Drug: Oxaliplatin · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Other: Placebo
Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD in the absence of unacceptable toxicity.
Drug: Oxaliplatin · Drug: Duloxetine Hydrochloride · Drug: Duloxetine · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Patients in Phase III receive placebo PO QD in the absence of unacceptable toxicity.
Drug: Oxaliplatin · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Other: Placebo
Given standard of care oxaliplatin
Given PO
Given PO
Ancillary studies
Ancillary studies
Given PO
Prevention of sensory oxaliplatin-induced peripheral neuropathy (OIPN) response (Phase II)
Will be measured using 6 individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet). For each of the 6 individual questions, patients are asked to select 1 of 4 choices regarding how each of the sensory symptoms had affected them during the preceding week: 1 = Not at all, 2 = A little, 3 = Quite a bit, and 4 = Very much. Response will be defined as a patient reporting a highest score of ≤ 2 at any time during oxaliplatin exposure, including 1 month post-oxaliplatin treatment without discontinuing the study due to sensory oxaliplatin-induced peripheral neuropathy. The proportion of responders within each arm will be estimated by the number of responders divided by the total number of evaluable patients. Two-sided 90% exact confidence intervals for the true response proportion will be calculated according to the approach of Clopper and Pearson.
Time frame: Up to 1 month post-oxaliplatin treatment
Prevention of sensory oxaliplatin-induced peripheral neuropathy (OIPN) response (Phase III)
Will be measured using 6 individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the distal extremities. For each of the 6 questions, patients are asked to select 1 of 4 choices regarding how each of the sensory symptoms had affected them during the preceding week: 1=Not at all, 2=A little, 3=Quite a bit, and 4=Very much. Response will be defined as a patient reporting a highest score of ≤ 2 at any time during oxaliplatin exposure, including 1 month post-oxaliplatin treatment without discontinuing the study due to sensory OIPN. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have completed the 6 QLQCIPN20 sensory symptom items on at least 1 occasion during oxaliplatin treatment, including 1 month post-oxaliplatin treatment. The Fisher exact test will be used for a between-arm comparison of the proportion of responders.
Time frame: Up to 1 month post-oxaliplatin treatment
Chronic neuropathic pain response (Phase III)
Response will be defined as a 7-day average of chronic neuropathic pain (on the average) ≤ 3 on a 0 (no pain) to 10 (pain as bad as you can imagine) scale 1 month after oxaliplatin treatment, which is obtained from the 7-day chronic neuropathy pain diary. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have completed the 7-day chronic neuropathy pain diary on at least 3 of the 7 days 1 month after the last oxaliplatin dose. The Fisher exact test will be used for a between-arm comparison of the proportion of responders.
Time frame: Up to 1 month after oxaliplatin treatment
Incidence of adverse events, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia (Phase II)
The constellation of adverse events as scored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 will be summarized within arms by reporting the number and percentages of patients. The proportion of each of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using NCI CTCAE v 5.0 will be estimated within arms with the exact 90% confidence interval.
Time frame: Up to 1 month post-oxaliplatin treatment
Serially measured total sensory neuropathy scores (Phase III)
The sequence of the total sensory neuropathy scores for each patient will be measured from the Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questionnaire, measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment. The corresponding area under the curve will be computed for each arm based on estimated parameters from a repeated-measures (means) mixed model and compared. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have a total sensory neuropathy score on at least 1 occasion during oxaliplatin treatment, including 1 month post-oxaliplatin treatment.
Time frame: Up to 1 month post-oxaliplatin treatment
Serially measured patient reported on the average pain scores (Phase III)
For each patient, the total sensory neuropathy score is calculated by summing the 6 individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet) and ranges from 1 to 24, where higher numbers indicate more severe symptoms. The sequence of the total sensory neuropathy scores for each patient will be measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxalipatin treatment. The corresponding area under the curve will be computed for each arm based on estimated parameters from a repeated-measures (means) mixed model and compared. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have a total sensory neuropathy score on at least 1 occasion during oxaliplatin treatment, including 1 month post-oxaliplatin treatment.
Time frame: Up to 1 month post-oxaliplatin treatment
Incidence of adverse events, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia (Phase III)
The constellation of adverse events as scored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 will be summarized within arms by reporting the number and percentages of patients. The proportion of each of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using NCI CTCAE v5.0 will be estimated within arms with the exact 95% confidence interval.
Time frame: Up to 1 month post-oxaliplatin treatment
Showing the first 100 of 793 sites across 2 countries. Choose a country and city above to see the rest.
This study is active, not recruiting, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Duloxetine
Alliance for Clinical Trials in Oncology →