Metastatic Colorectal Cancer (mCRC)
Conditions
Keywords
REGIRI, regorafenib, irinotecan
Brief summary
Patients with metastatic colorectal cancer (mCRC) who have received all approved standard treatments (except Regorafenib and Lonsurf) no longer have treatment options available while maintaining a good performance status which would allow them to receive a new treatment
Detailed description
A Phase II randomized trial compared Nexiri (Nexavar® + Irinotecan) vs irinotecan or versus Sorafenib (Nexavar®). The patients treated with Irinotecan or Sorafenib alone could receive NEXIRI combination after progression (crossover to Nexiri). Regorafenib, which is an oral signal deactivation agent with a chemical structure very similar to Sorafenib, is a standard treatment in heavily pretreated mCRC patients since the results of CORRECT study which compared Regorafenib to placebo on overall survival. Sorafenib isn't approved in mCRC so the objective of this NEXT-REGIRI trial is compared REGIRI combination (Regorafenib-Irinotecan) to Regorafenib alone in a phase III trial in patients in progression after having received all standard treatments and bearing genotype A/A of cyclin D1. The study's hypothesis is that regorafenib could have effects similar to those of sorafenib.
Interventions
DRUGRegorafenib
regorafenib tab 40 mg i.e 160 mg/day
DRUGIrinotecan
irinotecan 120 mg/m2 cycle 1, 150 mg/m2 cycle 2, 180 mg/m2 cycle 3 and more
Sponsors
Institut du Cancer de Montpellier - Val d'Aurelle
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent obtained before any study specific procedures * Male or female ≥ 18 years of age * Histological documentation of adenocarcinoma of the colon or rectum * Patients with metastatic colorectal cancer * Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti Vascular endothelial growth factor (VEGF) therapy and an anti Epithelial Growth Factor Receptor (EGFR) therapy (for RAS wild-type tumors) * Eastern Cooperative Oncology Group (ECOG) performance status ≤1 * Life expectancy of at least 3 months * Patients with A/A cycline D1 (CCND1) genotype of rs603965 CCND1 * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Amylase and lipase ≤1.5 x Upper Limit Normal (ULN),Total bilirubin ≤ 1.5 x ULN,Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement for their cancer and/or have bone metastases), Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3. Transfusion to meet the inclusion criterion, Serum creatinine ≤ 1.5 x ULN * International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care * Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment * Women of childbearing potential and men must agree to use adequate contraception before entering the study until at least respectively 7 months and 4 months after the last study drug administration of Regorafenib and respectively 6 months and 3 months after the last study drug administration of Irinotecan. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.
Exclusion criteria
* Patients with A/G or G/G cycline d1 (CCND1) genotype of rs603965 CCND1 * Prior treatment with regorafenib or sorafenib * Prior treatment with TAS 102 * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug * Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug * Congestive heart failure ≥ New York Heart Association (NYHA) class 2 * Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) * Myocardial infarction less than 6 months before start of study drug * Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) * Uncontrolled hypertension. (Systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management) * Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea) * Ongoing infection \> Grade 2 NCI-CTCAE V5.0 * Known history of human immunodeficiency virus (HIV) infection * Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy * Patients with seizure disorder requiring medication * History of organ allograft * Patients with evidence or history of any bleeding diathesis, irrespective of severity * Any hemorrhage or bleeding event ≥ NCI-CTC V5.0 Grade 3 within 4 weeks prior to the start of study medication * Non-healing wound, ulcer, or bone fracture * Dehydration NCI-CTCAE V5.0 Grade ≥ 1 * Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results * Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation * Any illness or medical conditions that are unstable or could * jeopardize the safety of the subject and his/her compliance in the study * Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (\> 3.5g/24 hours) * Patients unable to swallow oral medications * Any malabsorption condition * Chronic inflammatory bowel disease and / or bowel obstruction * Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity ≤ Grade 2 * Concomitant participation or participation within the last 30 days in another clinical trial * Systemic anticancer therapy during this trial or within 4 weeks before randomization * Concomitant intake of st John's wort * Live attenuated vaccines are prohibited 10 days before the treatment, during the treatment and 6 months after the termination of treatment * History of gastrointestinal fistula or perforation * Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival | Up to 36 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Deterioration | Up to 36 months | — |
| Number of Participants With Disease Control Rate | Through study completion, up to 14 months | — |
| Progression-free Survival (PFS) | Up to 36 months | — |
| Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Up to 36 months | — |
| Quality of Life Questionnaire | Questionnaire is assessed until 16 weeks (baseline, 8 weeks and 16 weeks) | The Quality of Life questionnaire (QLQ-C30) is a 30-item instrument designed to measure quality of life in all cancer patients. The QLQ-C30 incorporates five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia and diarrhea) and perceived financial impact of the disease. Score 0 to 100 for all subscales. * Functional scale : 0 the worst outcome, 100 is the best outcome, * Symptomatic scale : 0 the best outcome, 100 is the worst outcome Global functioning measures how much a person's symptoms affect their day-to-day life and role functioning assesses a patient's ability to perform daily activities, leisure time activities, and work on a scale of 0 to 100 (0 the worst outcome and 100 the best outcome). |
| Number of Patients With an Objective Response Rate | Through treatment completion, up to 14 months | — |
Countries
France
Participant flow
Recruitment details
Patients were recruited at 11 academic medical centers between March 2019 (first patient screened but non randomized) and august 2024.The first patient was randomized on September 18, 2019 and the last patient was randomized in march 2024.
Pre-assignment details
After enrollment, a screening was carried out according to the polymorphism (A870A rs603965) of cyclin D1, a protein involved in cell cycle regulation.Of 377 enrolled patients, 66 patients met selection criteria and were randomized to the study.In the protocol, we had planned to randomize 78 patients, but we had also specified that endpoints could be analyzed as soon as 55 events (deaths) were reached (i.e when one of the two is reached first).
Participants by arm
| Arm | Count |
|---|---|
| Irinotecan + Regorafenib (REGIRI) irinotecan (180 mg/m2) at day1 of each cycle + regorafenib (160 mg/day) from day 2 to day 8
Regorafenib: regorafenib tab 40 mg i.e 160 mg/day
Irinotecan: irinotecan 120 mg/m2 cycle 1, 150 mg/m2 cycle 2, 180 mg/m2 cycle 3 and more | 33 |
| Regorafenib Regorafenib (160 mg/day) for 3 weeks followed by 1 week off
Regorafenib: regorafenib tab 40 mg i.e 160 mg/day | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No treatment due to progression disease | 0 | 1 |
| Overall Study | No tumoral evaluation due to progression disease | 6 | 3 |
Baseline characteristics
| Characteristic | Total | Irinotecan + Regorafenib (REGIRI) | Regorafenib |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 16 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 17 Participants | 21 Participants |
| Age, Continuous | 64 years | 65 years | 64 years |
| Body Mass Index (BMI) | 24.6 kg/m² | 24.4 kg/m² | 25.3 kg/m² |
| Carbohydrate Antigen 19-9 (CA 19-9) Biomarker | 89 U/ml | 98 U/ml | 68 U/ml |
| Carcinoembryonic antigen (CEA) Biomarker | 52.75 ng/ml | 57.1 ng/ml | 46.1 ng/ml |
| FEMALE WEIGHT | 61.3 KG | 56.1 KG | 65.2 KG |
| Genotype of cycline D1 (polymorphism A/A) | 66 participants | 33 participants | 33 participants |
| Location of metastases Distant lymph nodes | 8 participants | 4 participants | 4 participants |
| Location of metastases Liver | 52 participants | 25 participants | 27 participants |
| Location of metastases Lung | 26 participants | 12 participants | 14 participants |
| Location of metastases Other (ovaries, adrenal glands, peritoneum) | 4 participants | 2 participants | 2 participants |
| Location of metastases Peritoneum | 13 participants | 10 participants | 3 participants |
| Location of primary tumor Left colon | 16 participants | 9 participants | 7 participants |
| Location of primary tumor Recto-sigmoid junction | 13 participants | 6 participants | 7 participants |
| Location of primary tumor Rectum | 18 participants | 9 participants | 9 participants |
| Location of primary tumor Right colon | 15 participants | 8 participants | 7 participants |
| Location of primary tumor transverse colon | 4 participants | 1 participants | 3 participants |
| lymph-node removal no | 31 participants | 14 participants | 17 participants |
| lymph-node removal yes | 35 participants | 19 participants | 16 participants |
| MALE WEIGHT | 77.5 KG | 75.2 KG | 82.6 KG |
| Microsatellite Stability (MSS) Status Missing | 8 participants | 4 participants | 4 participants |
| Microsatellite Stability (MSS) Status Mutant MSS (microsatellite stability biomarker) | 58 participants | 29 participants | 29 participants |
| Number of metastatic sites 1 metastatic site | 36 participants | 18 participants | 18 participants |
| Number of metastatic sites 2 metastatic sites | 24 participants | 11 participants | 13 participants |
| Number of metastatic sites 3 metastatic sites | 5 participants | 3 participants | 2 participants |
| Number of metastatic sites 4 metastatic sites | 1 participants | 1 participants | 0 participants |
| Number of patients with invaded nodes | 35 Participants | 19 Participants | 16 Participants |
| Number of patients with nodes removed | 35 Participants | 19 Participants | 16 Participants |
| Ongoing signs and symptoms no | 21 participants | 11 participants | 10 participants |
| Ongoing signs and symptoms yes | 45 participants | 22 participants | 23 participants |
| pM from TNM classification given by pathologist M0 (absence of metastasis) | 10 participants | 6 participants | 4 participants |
| pM from TNM classification given by pathologist M1 (presence of metastasis) | 42 participants | 22 participants | 20 participants |
| pM from TNM classification given by pathologist MX (unknown) | 14 participants | 5 participants | 9 participants |
| pN (node) from TNM classification given by pathologist pN0 (no lymph node invaded) | 10 participants | 3 participants | 7 participants |
| pN (node) from TNM classification given by pathologist pN1 (1 to 3 lymph nodes invaded) | 19 participants | 12 participants | 7 participants |
| pN (node) from TNM classification given by pathologist pN2 (> 4 lymph nodes invaded) | 17 participants | 8 participants | 9 participants |
| pN (node) from TNM classification given by pathologist pNx (unknown) | 20 participants | 10 participants | 10 participants |
| Previous surgery number 0 | 16 participants | 8 participants | 8 participants |
| Previous surgery number 1 | 22 participants | 13 participants | 9 participants |
| Previous surgery number 2 | 24 participants | 12 participants | 12 participants |
| Previous surgery number 3 | 3 participants | 0 participants | 3 participants |
| Previous surgery number 4 | 1 participants | 0 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 66 Participants | 33 Participants | 33 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| RAt Sarcoma virus (RAS) Status Mutant RAS | 37 participants | 18 participants | 19 participants |
| RAt Sarcoma virus (RAS) Status wild RAS | 29 participants | 15 participants | 14 participants |
| Region of Enrollment France | 66 participants | 33 participants | 33 participants |
| Sex: Female, Male Female | 30 Participants | 12 Participants | 18 Participants |
| Sex: Female, Male Male | 36 Participants | 21 Participants | 15 Participants |
| Significant medical and surgical history no | 9 participants | 3 participants | 6 participants |
| Significant medical and surgical history yes | 57 participants | 30 participants | 27 participants |
| Tumor (T) from TNM classification given by pathologist T1 (tumor invading the submucosa) | 1 participants | 1 participants | 0 participants |
| Tumor (T) from TNM classification given by pathologist T2 (tumor invading the muscularis) | 3 participants | 0 participants | 3 participants |
| Tumor (T) from TNM classification given by pathologist T3 (tumor invading the subserosa) | 24 participants | 17 participants | 7 participants |
| Tumor (T) from TNM classification given by pathologist T4 (tumor perforating the peritoneum or invading other organs) | 20 participants | 7 participants | 13 participants |
| Tumor (T) from TNM classification given by pathologist Tis (in situ carcinoma) | 1 participants | 0 participants | 1 participants |
| Tumor (T) from TNM classification given by pathologist Tx (unknown) | 17 participants | 8 participants | 9 participants |
| Type of adenocarcinoma Colloide adenocarcinoma | 2 participants | 2 participants | 3 participants |
| Type of adenocarcinoma LIEBERKUHNIEN adenocarcinoma | 60 participants | 27 participants | 33 participants |
| Type of adenocarcinoma Other adenocarcinoma | 4 participants | 4 participants | 0 participants |
| v-RAF murine sarcoma viral oncogene homolog B (BRAF) Status Missing | 12 participants | 3 participants | 9 participants |
| v-RAF murine sarcoma viral oncogene homolog B (BRAF) Status Mutant BRAF | 2 participants | 1 participants | 1 participants |
| v-RAF murine sarcoma viral oncogene homolog B (BRAF) Status Wild BRAF | 52 participants | 29 participants | 23 participants |
| World Health Organization (WHO) status performance index WHO=0 | 25 participants | 10 participants | 18 participants |
| World Health Organization (WHO) status performance index WHO=1 | 41 participants | 23 participants | 18 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 33 | 27 / 33 |
| other Total, other adverse events | 33 / 33 | 32 / 33 |
| serious Total, serious adverse events | 21 / 33 | 20 / 33 |
Outcome results
Primary
Overall Survival
Time frame: Up to 36 months
Population: Population per-protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Overall Survival | 9 Month |
| Regorafenib | Overall Survival | 5.5 Month |
Comparison: To show an increase of median overall survival from 7 to 15 months (30% to 57% rates, respectively), with a HR=0.47 and a power of 80% and alpha=5%, 55 events are required for the 78 patients to be randomized considering 15% additional patients for lost to follow-up.p-value: 0.533495% CI: [0.7, 1.98]Log Rank
p-value: 0.889495% CI: [0.59, 1.82]Chi-squared
Secondary
Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient)
Time frame: Up to 36 months
Population: Intention to treat
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 2 | 13 Participants |
| Irinotecan + Regorafenib (REGIRI) | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 4 | 4 Participants |
| Irinotecan + Regorafenib (REGIRI) | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 3 | 9 Participants |
| Irinotecan + Regorafenib (REGIRI) | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 5 | 3 Participants |
| Irinotecan + Regorafenib (REGIRI) | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 1 | 4 Participants |
| Regorafenib | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 5 | 0 Participants |
| Regorafenib | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 1 | 2 Participants |
| Regorafenib | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 2 | 8 Participants |
| Regorafenib | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 3 | 21 Participants |
| Regorafenib | Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient) | Grade 4 | 1 Participants |
Secondary
Number of Participants With Disease Control Rate
Time frame: Through study completion, up to 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Number of Participants With Disease Control Rate | 20 Participants |
| Regorafenib | Number of Participants With Disease Control Rate | 8 Participants |
p-value: 0.001Fisher Exact
Secondary
Number of Patients With an Objective Response Rate
Time frame: Through treatment completion, up to 14 months
Population: Population Per protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Number of Patients With an Objective Response Rate | 2 Participants |
| Regorafenib | Number of Patients With an Objective Response Rate | 0 Participants |
p-value: 0.001Fisher Exact
Secondary
Progression-free Survival (PFS)
Time frame: Up to 36 months
Population: Intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Progression-free Survival (PFS) | 3.6 month |
| Regorafenib | Progression-free Survival (PFS) | 1.9 month |
p-value: 0.110495% CI: [0.4, 1.11]Log Rank
p-value: 0.116595% CI: [0.4, 1.11]Chi-squared
Secondary
Quality of Life Questionnaire
The Quality of Life questionnaire (QLQ-C30) is a 30-item instrument designed to measure quality of life in all cancer patients. The QLQ-C30 incorporates five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia and diarrhea) and perceived financial impact of the disease. Score 0 to 100 for all subscales. * Functional scale : 0 the worst outcome, 100 is the best outcome, * Symptomatic scale : 0 the best outcome, 100 is the worst outcome Global functioning measures how much a person's symptoms affect their day-to-day life and role functioning assesses a patient's ability to perform daily activities, leisure time activities, and work on a scale of 0 to 100 (0 the worst outcome and 100 the best outcome).
Time frame: Questionnaire is assessed until 16 weeks (baseline, 8 weeks and 16 weeks)
Population: The number of patients differs from the ITT population because some patients have not completed the questionnaires. Therefore the analysis is carried out on a smaller population, those who responded to the questionnaires. The table below shows the median scores of scales ranging from 0 to 100.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | INSOMNIA AT BASELINE | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | PHYSICAL FUNCTIONING AT BASELINE | 93 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | ROLE FUNCTIONING AT BASELINE | 100 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | EMOTIONAL FUNCTIONING AT BASELINE | 83 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | COGNITIVE FUNCTIONING AT BASELINE | 83 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | SOCIAL FUNCTIONING AT BASELINE | 100 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | ASTHENIA AT BASELINE | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | NAUSEA AND VOMITING AT BASELINE | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | PAIN AT BASELINE | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | DYSPNEA AT BASELINE | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | GLOBAL HEALTH STATUS AT BASELINE | 63 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | APPETITE LOSS AT BASELINE | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | DIARRHEA AT BASELINE | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | FINANCIAL DIFFICULTIES AT BASELINE | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | GLOBAL HEALTH STATUS AT 8 WEEKS | 67 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | PHYSICAL FUNCTIONING AT 8 WEEKS | 87 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | ROLE FUNCTIONING AT 8 WEEKS | 83 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | EMOTIONAL FUNCTIONING AT 8 WEEKS | 83 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | COGNITIVE FUNCTIONING AT 8 WEEKS | 83 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | SOCIAL FUNCTIONING AT 8 WEEKS | 83 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | ASTHENIA AT 8 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | NAUSEA AND VOMITING AT 8 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | PAIN AT 8 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | DYSPNEA AT 8 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | INSOMNIA AT 8 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | APPETITE LOSS AT 8 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | DIARRHEA AT 8 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | FINANCIAL DIFFICULTIES AT 8 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | GLOBAL HEALTH STATUS AT 16 WEEKS | 58 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | PHYSICAL FUNCTIONING AT 16 WEEKS | 80 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | ROLE FUNCTIONING AT 16 WEEKS | 67 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | EMOTIONAL FUNCTIONING AT 16 WEEKS | 75 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | COGNITIVE FUNCTIONING AT 16 WEEKS | 100 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | SOCIAL FUNCTIONING AT 16 WEEKS | 67 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | ASTHENIA AT 16 WEEKS | 44 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | NAUSEA AND VOMITING AT 16 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | PAIN AT 16 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | DYSPNEA AT 16 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | INSOMNIA AT 16 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | APPETITE LOSS AT 16 WEEKS | 0 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | DIARRHEA AT 16 WEEKS | 33 Units on a scale |
| Irinotecan + Regorafenib (REGIRI) | Quality of Life Questionnaire | FINANCIAL DIFFICULTIES AT 16 WEEKS | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | EMOTIONAL FUNCTIONING AT 16 WEEKS | 79 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | GLOBAL HEALTH STATUS AT BASELINE | 67 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | NAUSEA AND VOMITING AT 8 WEEKS | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | PHYSICAL FUNCTIONING AT BASELINE | 75 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | APPETITE LOSS AT 16 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | ROLE FUNCTIONING AT BASELINE | 75 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | PAIN AT 8 WEEKS | 67 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | EMOTIONAL FUNCTIONING AT BASELINE | 92 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | COGNITIVE FUNCTIONING AT 16 WEEKS | 92 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | COGNITIVE FUNCTIONING AT BASELINE | 100 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | DYSPNEA AT 8 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | SOCIAL FUNCTIONING AT BASELINE | 75 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | DYSPNEA AT 16 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | ASTHENIA AT BASELINE | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | INSOMNIA AT 8 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | NAUSEA AND VOMITING AT BASELINE | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | SOCIAL FUNCTIONING AT 16 WEEKS | 75 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | PAIN AT BASELINE | 17 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | APPETITE LOSS AT 8 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | DYSPNEA AT BASELINE | 17 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | FINANCIAL DIFFICULTIES AT 16 WEEKS | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | INSOMNIA AT BASELINE | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | DIARRHEA AT 8 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | APPETITE LOSS AT BASELINE | 17 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | ASTHENIA AT 16 WEEKS | 44 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | DIARRHEA AT BASELINE | 17 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | FINANCIAL DIFFICULTIES AT 8 WEEKS | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | FINANCIAL DIFFICULTIES AT BASELINE | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | INSOMNIA AT 16 WEEKS | 50 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | GLOBAL HEALTH STATUS AT 8 WEEKS | 50 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | GLOBAL HEALTH STATUS AT 16 WEEKS | 58 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | PHYSICAL FUNCTIONING AT 8 WEEKS | 40 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | NAUSEA AND VOMITING AT 16 WEEKS | 0 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | ROLE FUNCTIONING AT 8 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | PHYSICAL FUNCTIONING AT 16 WEEKS | 63 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | EMOTIONAL FUNCTIONING AT 8 WEEKS | 83 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | DIARRHEA AT 16 WEEKS | 33 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | COGNITIVE FUNCTIONING AT 8 WEEKS | 100 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | ROLE FUNCTIONING AT 16 WEEKS | 67 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | SOCIAL FUNCTIONING AT 8 WEEKS | 83 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | PAIN AT 16 WEEKS | 8 Units on a scale |
| Regorafenib | Quality of Life Questionnaire | ASTHENIA AT 8 WEEKS | 78 Units on a scale |
Secondary
Time to Deterioration
Time frame: Up to 36 months
Population: Intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan + Regorafenib (REGIRI) | Time to Deterioration | 4.6 month |
| Regorafenib | Time to Deterioration | 2.1 month |
p-value: 0.242595% CI: [0.26, 1.42]Log Rank
p-value: 0.251995% CI: [0.26, 1.42]Chi-squared