Advanced and Metastatic Solid TumorPhase 1REGONIVONCT03406871
Regorafenib and Nivolumab Simultaneous Combination Therapy
A Phase 1 study testing Regorafenib and Nivolumab in people with Advanced and Metastatic Solid Tumor, run by Kohei Shitara at 1 site in Japan.
Trial summary
the efficacy and safety ofhe use of regorafenib in combination with nivolumab Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced and Metastatic Solid Tumor
- What is being tested?
- Regorafenib and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteJapan
- Study dates
- 15 Jan 2018to 15 Dec 2020
- Phase
- Phase 1
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who provided written informed consent to be subjects in this trial
- Patients at least 20 years of age on the day of providing consent
- Dose-escalation cohort: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors.
- Expansion cohort: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors (gastric, colorectal, or hepatocellular cancer).
- Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Patients capable of taking oral medication
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- Patients with evaluable or measurable lesions as per RECIST version 1.1
- Patients with adequate organ function at the time of enrollment as defined below:
- Neutrophil count ≥1500mm3
- Platelet count ≥10.0 × 104/mm3
- Hemoglobin (Hb) ≥ 9 g/dL,
- aspartate transaminase (AST), alanine transaminase (ALT) ≤100 U/L (≤100 U/L in patients with Hepatocellular carcinoma, ≤250 U/L in patients with liver metastasis)
- Total bilirubin ≤1.5-mg /dL
- Creatinine ≤1.5--mg /dL
- Lipase ≤ 80 IU/L
- Urinary protein: It satisfies one of the following (if any of the inspection criteria are satisfied, other examination may not be carried out) (i) urinary protein (test paper method) is 2+ or less (ii) Urine Protein Creatinine(UPC) ratio <3.5 (iii) 24-hour urine protein was measured, urinary protein ≦ 3500 mg
- Prothrombin time (PT)- International normalized ratio(INR): ≤ 1.5 (≦ 3.0 in case of anticoagulant administration)
- For women who are likely to become pregnant (including those without menstruation due to medical reasons such as chemical menopause) Note 1, we agreed to double contraceptive Note 2 for at least 5 months from consent acquisition patient to the final administration of the investigational product. Also, patients who agreed not to breast feeding for at least 5 months from acquiring consent to the final investigational drug administration.
- For men, patients agreeing to double contraceptive for at least 7 months from the time of starting investigational drug administration to the final investigational drug administration.
- Note 1): A woman who is likely to become pregnant is a woman who has experienced menarche and is not undergoing sterilization surgery (such as hysterectomy, bilateral salpingo ligation or bilateral oophorectomy), a woman without menopause Everything is included. The definition after menopause shall be amenorrhea continuously for 12 months or more even though there is no noteworthy reason. Women who are using oral contraceptives or mechanical contraceptive methods (such as intrauterine contraceptive devices or barrier methods) are considered to be pregnant.
- Note 2): With regard to contraception, it is necessary to use two of the vasectomy or condom of a male patient or male male, the uterine tube ligation of a female patient or the other woman, a contraceptive pessary, an intrauterine contraceptive device or an oral contraceptive I need to agree to heavy contraception.
Who cannot join
- Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone therapy, or immunotherapy <2 weeks before enrollment. Immune checkpoint blockade as pretreatment is permitted.
- Patients with a history of taking regorafenib.
- Patients with hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents
- Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment
- Patients with a large amount of pleural effusion or ascites requiring drainage.
- Patients with a ≥grade 3 active infection according to NCI-CTCAE version 4.03
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- Patients with symptomatic brain metastasis
- Patients with partial or complete gastrointestinal obstruction
- Patients with interstitial lung disease with symptoms or signs of activity
- Patients who test positive for either anti-HIV-1 antibodies, anti-HIV-2 antibodies, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies*
- Patients who test positive for either anti-Hepatitis B surface(HBs) or anti- Hepatitis B core(HBc) antibodies, and those who have hepatitis B virus (HBV)-DNA measurements greater than the detection sensitivity will also be excluded.
- (However, patients with hepatocellular carcinoma in the expansion cohort will not be excluded even if they test positive for HBsAg and anti-HCV antibodies.)
- Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease
- Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy) or immunosuppressants, or who have received such a therapy <14 days before enrollment in the present study
- Patients with a history or findings of ≥grade III congestive heart failure according to the New York Heart Association functional classification
- Patients with a seizure disorder who require pharmacotherapy
- Patients who had grade 3 or higher bleeding during 4 weeks before enrollment
- Patients undergoing major surgery (thoracotomy or laparotomy, etc.), laparotomy biopsy, trauma within 28 days before registration. The same day of the week before 4 weeks can be registered (However, in case of an artificial anastomosis without intestinal resection, it shall be within 14 days before registration).
- Patients with non-healing wound, non-healing ulcer, or non-healing bone fracture.
- Patients with a history of hypersensitivity to any of the study drugs, similar drugs, or excipients.
- Women who are pregnant or breastfeeding, or with the potential for pregnancy.
- Definition of DLT:
- In principle, a DLT was any of the following Adverse Drug Reactions (ADRs) observed during Cycle 1 (28 days), which was the DLT evaluation period, and was finally determined after discussion in the coordinating committee. According to need, the opinion of the data and safety monitoring committee was to be sought.
- Hematological toxicity Grade 4 neutropenia lasting for more than 7 days. Neutrophil count of <1000/mm3 with a fever of ≥38.0°C. Grade 4 thrombocytopenia or thrombocytopenia with bleeding requiring platelet transfusion. Grade 3 thrombocytopenia with bleeding.
- Non-hematological toxicity. Grade 3 or higher non-hematological toxicity. However, non-hematological toxicities meeting any of the following criteria are classified as DLTs only when the investigator determines it impossible to continue the study even with supportive therapy.
- Grade 3 diarrhea, nausea, vomiting, or anorexia lasting for at least 5 days.
- Grade 3 or higher electrolyte abnormality lasting for at least 7 days.
- Grade 3 or higher skin toxicity lasting for at least 7 days.
- AST or ALT increased ≥5 to 8 times the upper limit of the institutional reference range that does not improve to ≤5 times the upper limit of the institutional reference range within 7 days, with T-Bil increased ≤2 times the upper limit of the institutional reference range.
- AST or ALT increased ≥5 to 8 times the upper limit of the institutional reference range, with T-Bil increased ≥2 times the upper limit of the institutional reference range.
- AST or ALT increased ≥8 times the upper limit of the institutional reference range.
- T-Bil increased ≥3 times the upper limit of the institutional reference range.
- Grade 3 or higher immune-related AEs lasting for at least 8 days even with steroid therapy.
- Overall The case in which 70% of the planned dose of regorafenib was not administered due to toxicities during the DLT evaluation period, or the case in which the specified number of nivolumab doses was not administered.
- Patients evaluated for DLT:
- At least 3 patients were enrolled at each dose level, and the presence or absence of a DLT was evaluated during the DLT evaluation period.
- When there were patients not patient to the assessment for proceeding to the next dose level, additional patients were to be enrolled to allow the DLT evaluation specified in Section "6.1.3 Definition of DLT." Patients enrolled who met any of the following criteria were excluded from the DLT analysis set.
- Patients in whom regorafenib was not administered for 10 days or longer during Cycle 1 for reasons other than toxicity.
- Patients in whom no dose of nivolumab was administered during Cycle 1 for reasons other than toxicity.
- Patients in whom adequate data for DLT evaluation were not obtained due to missing essential testing or other reasons.
- Whether to include the following patients in the DLT analysis set was determined by discussion in the coordinating committee: patients who had treatment interruption with regorafenib and nivolumab during Cycle 1 for reasons other than Adverse Events (AEs) or patients who were not allowed to initiate Cycle 2 due to toxicities other than DLT.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Regorafenib and Nivolumab Simultaneous Combination Therapy for Advanced and Metastatic Solid Tumors: Phase I Clinical Trial
the efficacy and safety ofhe use of regorafenib in combination with nivolumab
Read the detailed description
The present trial consists of a dose-escalation cohort to verify the tolerability of nivolumab and regorafenib when used in combination for patients with solid tumors, and to examine the clinical recommended dose(RD). The trial also consists of an expansion cohort to examine the safety and efficacy when the clinical RD is administered for several advanced solid tumors.
In the dose-escalation cohort, three patients with solid tumors will be administered 3.0 mg/kg of nivolumab once every 2 weeks and regorafenib daily for 21days, with a 1-week washout period at dose of 80 mg (level 1), 120 mg (level 2), or 160 mg (level 3). As a general rule, one cycle will last 28 days (day 1-29); however, in the event of treatment prolongation, the cycle period will be extended. The Dose Limiting Toxicity(DLT) evaluation period will be 28 days. Furthermore, for each level, three additional subjects will be added depending on the state of DLT.
In the expansion cohort, the target subject sample will consist of approximately 30 patients who will be administered 3.0 mg/kg of nivolumab once every 2 weeks, and the clinical RD of regorafenib will be determined in the dose-escalation cohort.
- Conditions
- Advanced and Metastatic Solid Tumor
- Being tested
- Regorafenib, Nivolumab
- Keywords
- Regorafenib, Nivolumab, Phase I clinical trial
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called Identification code of the investigational drug; BAY73-4506
One course will last 28 days. Oral administration for 21 consecutive days, with a 1-week washout period. As for the expansion cohort, implemented using the RD estimated in the dose-escalation cohort.
NivolumabDrug
Also called Identification code of the investigational drug; BMS-936558, MDX1106, ONO-4538
One course will last 28 days. Given once every 2 weeks at a dose of 3.0 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| Level 1 | Active comparator | Regorafenib: Oral administration at a dose of 80 mg given once per day for 21 consecutive days, with a 1-week washout period.
Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg via an intravenous infusion.
When it is deemed that there is no problem with safety at the doses described above, tolerability will be verified at the level-2 dosages described below. Receives: Drug: Regorafenib; Drug: Nivolumab |
| Level 2 | Active comparator | Regorafenib: Oral administration at a dose of 120 mg/day for 21 consecutive days, with a 1-week washout period.
Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg.
When it is deemed that there is no problem with safety at the doses described above, tolerability will be verified at the level-3 dosages described below. Receives: Drug: Regorafenib; Drug: Nivolumab |
| Level 3 | Active comparator | Regorafenib: Oral administration at a dose of 160 mg/day for 21 consecutive days, with a 1-week washout period.
Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg.
After starting the trial, three cases are registered at level 1, and temporary case registration is suspended until safety evaluation of the first course is completed in all cases. If there are cases in which evaluation of DLT can not be performed properly, such as being canceled due to reasons other than safety during the course of the first course, the necessary number of cases is appropriately added to the administration level. Receives: Drug: Regorafenib; Drug: Nivolumab |
| Expansion cohort | Active comparator | After completion of the final DLT evaluation period of the subjects in the dose escalating cohort, the decision to move the subjects into the expansion cohort will be determined once it is decided, upon deliberation between the sponsor and the principal investigator, that there are no problems associated with moving on. Furthermore, the opinion of the Data and Safety Monitoring Committee (DSMC) can be sought as required .
Regarding the review of RD in the expansion cohort, please refer to "Analysis Population Description" in Primary Outcome Measures. Receives: Drug: Regorafenib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Dose Limiting Toxicity (DLT) for RD Determination
The procedure for DLT assessment was as follows:
- When DLT is observed in 1 out of 3 cases, 3 additional cases are added to the administration level.
- When DLT is observed in more than 2 of 3 cases, it is judged that the administration level exceeds Maximum Tolerated Dose (MTD).
- If the number of DLT is 1 case or less in 6 cases, shift to the next level.
- If MTD is exceeded, shift to the next lower level. At the relevant dose, if only 3 people are evaluating DLT, add 3 cases. When the number of DLT is 1 or less out of 6, the dose is defined as MTD and RD. If it is judged that Level 1 exceeds the MTD, review the dose or consider stopping the trial.
- MTD should be the highest dose level of DLT expression less than 1 in 6 cases. - After the RD was determined and the patient moved to the expansion cohort, G3 skin toxicity occurred, so based on the recommendation of the Data and Safety Monitoring Committee, the RD was reduced by one level and the trial was resumed.
Measured: 4 weeks
Secondary outcomes (5)
Objective Response Rate (ORR)
*Objective Response Rate is defined as the proportion of patients whose best overall response, as per the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 and immune-related RECIST (irRECIST), is either Complete Response (CR) or Partial Response (PR).
Measured: 2year
Progression-Free Survival(PFS)
*PFS is defined as the time from the enrollment date to either the date when disease progression is determined or the date of death from any cause, whichever came earlier.
The data were compiled according to the analysis plan outlined in the protocol. No analysis was conducted to determine efficacy by cancer type or dose level.
Measured: 6 months
Overall Survival(OS)
*OS is defined as the period from the date of enrollment to the date of death from any cause.
Surviving patients are censored on the last confirmation date of survival (confirmation of survival by telephone is permitted; the fact that survival is confirmed is to be recorded in the medical record, etc.).
Patients lost to follow-up are censored on the last date on which their survival is confirmed before being lost to follow-up.
The data were compiled according to the analysis plan outlined in the protocol. No analysis was conducted to determine efficacy by cancer type or dose level.
Measured: 2year
Disease Control Rate(DCR)
*DCR is defined as the proportion of patients whose best overall response assessed based on the RECIST guideline version 1.1 and irRECIST is any of CR, PR, or Stable Disease (SD).
The data were compiled according to the analysis plan outlined in the protocol. No analysis was conducted to determine efficacy by cancer type or dose level.
Measured: 2year
Adverse-Events
- The occurrences rate of each AE of the worst grade occurring in this study was evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 throughout the entire cycles will be calculated. Additionally, this study included a special note regarding abnormal laboratory values. If clinical signs and symptoms observed in this study were induced, the diagnosis and associated data were collected based on whether or not they were due to abnormal laboratory values. Therefore, for example, results of grading regarding liver dysfunction may differ between non-hematologic toxicity and laboratory values.
- Adverse-Events occurrences means "prevalence proportion" of any undesirable occurrence based on investigator's medical decision in this study.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start15 Jan 2018
- Primary completion15 Dec 2020
- Study completion15 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced and Metastatic Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kohei Shitara
- Sponsor type
- University, hospital or other
- Collaborators
- Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd.
- Responsible party
- Sponsor-investigator, Kohei Shitara, National Cancer Center Hospital East
- Investigators
- Kohei Shitara, Dr, Study chair, National Cancer Center Hospital East
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03406871
- Sponsor's protocol ID
- EPOC 1603 study
- Acronym
- REGONIVO
- Status last verified
- Dec 2024
- First submitted
- 12 Jan 2018
- Last updated
- 24 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Kuwata T, Togashi Y, Nishikawa H, Shitara K. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol. 2020 Jun 20;38(18):2053-2061. doi: 10.1200/JCO.19.03296. Epub 2020 Apr 28.
PubMed 32343640
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib and Nivolumab Simultaneous Combination Therapy for Advanced and Metastatic Solid Tumors: Phase I Clinical Trial
- ClinicalTrials.gov ID
- NCT03406871
- Acronym / sponsor ID
- REGONIVO / EPOC 1603 study
- Conditions
- Advanced and Metastatic Solid Tumor
- Keywords
- Regorafenib, Nivolumab, Phase I clinical trial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Kohei ShitaraUniversity, hospital or other
- Collaborators
- Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd.
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 15 Dec 2020 (actual)
- Study completion
- 15 Dec 2020 (actual)
- First posted
- 23 Jan 2018 (actual)
- Results
- Posted 24 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
the efficacy and safety ofhe use of regorafenib in combination with nivolumab
Detailed description
The present trial consists of a dose-escalation cohort to verify the tolerability of nivolumab and regorafenib when used in combination for patients with solid tumors, and to examine the clinical recommended dose(RD). The trial also consists of an expansion cohort to examine the safety and efficacy when the clinical RD is administered for several advanced solid tumors.
In the dose-escalation cohort, three patients with solid tumors will be administered 3.0 mg/kg of nivolumab once every 2 weeks and regorafenib daily for 21days, with a 1-week washout period at dose of 80 mg (level 1), 120 mg (level 2), or 160 mg (level 3). As a general rule, one cycle will last 28 days (day 1-29); however, in the event of treatment prolongation, the cycle period will be extended. The Dose Limiting Toxicity(DLT) evaluation period will be 28 days. Furthermore, for each level, three additional subjects will be added depending on the state of DLT.
In the expansion cohort, the target subject sample will consist of approximately 30 patients who will be administered 3.0 mg/kg of nivolumab once every 2 weeks, and the clinical RD of regorafenib will be determined in the dose-escalation cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Level 1 | Active comparator | Drug: Regorafenib, Drug: NivolumabRegorafenib: Oral administration at a dose of 80 mg given once per day for 21 consecutive days, with a 1-week washout period. Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg via an intravenous infusion. When it is deemed that there is no problem with safety at the doses described above, tolerability will be verified at the level-2 dosages described below. |
| Level 2 | Active comparator | Drug: Regorafenib, Drug: NivolumabRegorafenib: Oral administration at a dose of 120 mg/day for 21 consecutive days, with a 1-week washout period. Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg. When it is deemed that there is no problem with safety at the doses described above, tolerability will be verified at the level-3 dosages described below. |
| Level 3 | Active comparator | Drug: Regorafenib, Drug: NivolumabRegorafenib: Oral administration at a dose of 160 mg/day for 21 consecutive days, with a 1-week washout period. Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg. After starting the trial, three cases are registered at level 1, and temporary case registration is suspended until safety evaluation of the first course is completed in all cases. If there are cases in which evaluation of DLT can not be performed properly, such as being canceled due to reasons other than safety during the course of the first course, the necessary number of cases is appropriately added to the administration level. |
| Expansion cohort | Active comparator | Drug: Regorafenib, Drug: NivolumabAfter completion of the final DLT evaluation period of the subjects in the dose escalating cohort, the decision to move the subjects into the expansion cohort will be determined once it is decided, upon deliberation between the sponsor and the principal investigator, that there are no problems associated with moving on. Furthermore, the opinion of the Data and Safety Monitoring Committee (DSMC) can be sought as required . Regarding the review of RD in the expansion cohort, please refer to "Analysis Population Description" in Primary Outcome Measures. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients who provided written informed consent to be subjects in this trial
- Patients at least 20 years of age on the day of providing consent
- Dose-escalation cohort: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors.
- Expansion cohort: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors (gastric, colorectal, or hepatocellular cancer).
- Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Key exclusion criteria (41 listed)
- Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone therapy, or immunotherapy <2 weeks before enrollment. Immune checkpoint blockade as pretreatment is permitted.
- Patients with a history of taking regorafenib.
- Patients with hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents
- Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment
- Patients with a large amount of pleural effusion or ascites requiring drainage.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RegorafenibAlso: Identification code of the investigational drug; BAY73-4506One course will last 28 days. Oral administration for 21 consecutive days, with a 1-week washout period. As for the expansion cohort, implemented using the RD estimated in the dose-escalation cohort. | Drug | Expansion cohort, Level 1, Level 2, Level 3 |
| NivolumabAlso: Identification code of the investigational drug; BMS-936558, MDX1106, ONO-4538One course will last 28 days. Given once every 2 weeks at a dose of 3.0 mg/kg. | Drug | Expansion cohort, Level 1, Level 2, Level 3 |
Primary outcome
The Number of Dose Limiting Toxicity (DLT) for RD Determination
Time frame: 4 weeks
The procedure for DLT assessment was as follows: 1. When DLT is observed in 1 out of 3 cases, 3 additional cases are added to the administration level. 2. When DLT is observed in more than 2 of 3 cases, it is judged that the administration level exceeds Maximum Tolerated Dose (MTD). 3. If the number of DLT is 1 case or less in 6 cases, shift to the next level. 4. If MTD is exceeded, shift to the next lower level. At the relevant dose, if only 3 people are evaluating DLT, add 3 cases. When the number of DLT is 1 or less out of 6, the dose is defined as MTD and RD. If it is judged that Level 1 exceeds the MTD, review the dose or consider stopping the trial. 5. MTD should be the highest dose level of DLT expression less than 1 in 6 cases. - After the RD was determined and the patient moved to the expansion cohort, G3 skin toxicity occurred, so based on the recommendation of the Data and Safety Monitoring Committee, the RD was reduced by one level and the trial was resumed.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: 2year
Progression-Free Survival(PFS)
Time frame: 6 months
Overall Survival(OS)
Time frame: 2year
Disease Control Rate(DCR)
Time frame: 2year
Adverse-Events
Time frame: 2 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32343640Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Kuwata T, Togashi Y, Nishikawa H, Shitara K. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol. 2020 Jun 20;38(18):2053-2061. doi: 10.1200/JCO.19.03296. Epub 2020 Apr 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kohei Shitara, Dr study chair
National Cancer Center Hospital East
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Regorafenib and Nivolumab in people with Advanced and Metastatic Solid Tumor, run by Kohei Shitara at 1 site in Japan.
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 21 inclusion and 41 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 24 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. 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?
Yes. Results are posted in the registry (first posted 24 Jan 2025). 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?
The Number of Dose Limiting Toxicity (DLT) for RD Determination (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 NCT03406871, which also lists 1 linked publication.
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 24 Jan 2025.