Esophageal CancerPhase 1/2NCT03544736
Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (INEC)
A Phase 1/2 study testing Nivolumab, Radiotherapy and Chemotherapy in people with Esophageal Cancer, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer
- What is being tested?
- Nivolumab, Radiotherapy and Chemotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNorway
- Study dates
- 26 Apr 2018to 31 Dec 2040
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Three different cohorts of patients with esophageal cancer are studied.
- All of the following conditions must apply to the prospective patient at screening prior to receiving study treatment or any study related procedures (e.g.):
- Age > 18 years
- Patients should have previously untreated histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastroesophageal junction (GEJ), Siewert I, II or III
- Must be ambulatory with a performance status ECOG 0 or 1
- Adequate organ function based on clinical examination and lab values as defined in the below:
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- Absolute neutrophil count: ≥ 1,5 x109/L Platelets: ≥ 100 x109/L Hemoglobin: ≥ 9 x109/L Creatinine ≤ 1,5 upper limit normal (ULN) OR measured/calculated GFR≥60 mL/min Albumin ≥ 30 g/L Total bilirubin ≤ 1,5 ULN ASAT and ALAT ≤ 2,5 ULN, or ≤ 5 ULN for subjects with liver mets. International Normalized Ratio (INR) ≤ 1,5 ULN and Activated Partial Thromboplastin Time (TT) ≤ 1,5 ULN unless subject is receiving anticoagulant therapy. Such therapy (if indicated) should be converted to adequate therapy with low-molecular weight heparin such as Dalteparin before chemotherapy or treatment with IMP.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days prior to the start of study drug (screening phase). Women must not be breastfeeding.
- WOCBP should use highly effective adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug. Adequate methods are described in Appendix I.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception during the study treatment period and until 7 months after last dose of Nivolumab (see Appendix I).
- Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
- If Dysphagia score >2, a nasogastric feeding tube should be inserted during the aid of gastroscopy, and nasogastric tube feeding started before radiotherapy.
- In addition, specific criteria are defined for the three different patient cohorts below:
- Specific inclusion criteria - Cohort A
- Eligible for palliative fractionated radiotherapy of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
- Expected survival >3 months
- Not bulky disease, i.e. palliative radiotherapy towards the primary tumor is intended to palliate dysphagia and/or pain and systemic treatment could be delayed to AFTER protocol therapy if possible.
- Specific inclusion criteria - Cohort B
- Eligible for definitive chemoradiation of localized but inoperable esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
- Regional disease, i.e. no metastasis outside the radiation field (PTV).
- Considered candidate/ able to adhere to the intended chemoradiotherapy
- Specific inclusion criteria - Cohort C
- Eligible for neoadjuvant chemoradiotherapy and surgery of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
- Regional disease, i.e. no metastasis outside the radiation field (PTV).
- Considered candidate and able to adhere to the intended neoadjuvant chemoradiotherapy and planned surgery.
Who cannot join
- Patients will be excluded from the study if they meet any of the following criteria:
- Previous treatment with radiotherapy towards volumes within the thoracic cavity
- Previous treatment with any PD-1 or PD-L1/2 inhibitor
- Hypersensitivity to the investigational product or any of the drug formula contents
- Esophageal stenting
- T4b if infiltration into the aorta or the trachea
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- History of prior autoimmune disorders requiring systemic therapy (excluding Insulin or Thyroid replacement therapy)
- History of HIV 1 /2, Hepatitis B or C infection
- History of Immunodeficiency disorders (i.e. immunoglobulin deficiency or white blood cell lineage depletion disorders)
- Participation in any other interventional clinical trial with an investigational product
- History of prior malignancy within the last 5 years, excluding curatively treated basal cell or squamous cell carcinoma of the skin.
- Known history of brain metastases
- Need to use immunosuppressive drugs including, but not limited to: Glucocorticoids, everolimus, sirolimus, disease-modifying anti-rheumatic drugs (DMARDS)
- Positive pregnancy test (positive hCG blood test)
- Known allergy, hypersensitivity, or contraindication to the investigational product Nivolumab, or the drugs paclitaxel and docetaxel used in the standard chemoradiotherapy protocols (Cohorts B and C) or any components used in their preparation or has a contraindication to taxane therapy.
- Any reason why, in the opinion of the investigator, the patient should not participate.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (INEC-study) - a Phase I/II Trial
Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer
Read the detailed description
Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer.
Cohort A: Advanced/inoperable esophageal cancer, eligible for palliative radiotherapy of the primary tumor.
Cohort B: Inoperable esophageal cancer without metastases, eligible for definitive chemoradiotherapy Cohort C: Operable esophageal cancer eligible for neoadjuvant chemoradiotherapy
- Conditions
- Esophageal Cancer
- Being tested
- Nivolumab, Radiotherapy, Chemotherapy, Surgery
- Keywords
- Nivolumab, Immunotherapy
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Experimental: Nivolumab
RadiotherapyRadiation
Radiotherapy
ChemotherapyDrug
Also called Paclitaxel and Carboplatin
Chemotherapy
SurgeryProcedure or surgery
Surgery
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Subjects having palliative radiotherapy towards esophageal tumor will receive concomitant therapy With Nivolumab i.v. 240mg Q2W: first 6 patients, 360mg Q3W: Next 6 patients or 480mg Q4W: Last 6 patients, treatment to progression or up to 2 years of treatment.
Radiotherapy: 2 Gy / day, (5 fx/week) to a total of 20 - 50 Gy in 25fx (2-4Gy/fx) at the decision of the responsible physician. Receives: Drug: Nivolumab; Radiation: Radiotherapy |
| Cohort B | Experimental | Subjects receiving definitive chemoradiotherapy for esophageal cancer will receive concomitant therapy with Nivolumab 240mg Q2W, during RT, and continued with 480mg Q4W, treatment to progression or up to 1 year after completion of radiotherapy. 6 patients in total.
Chemotherapy: Paclitaxel i.v. 175mg/m2 and Carboplatin AUC5, then after 21 days Radiotherapy 1,8 Gy / day (5 fx/week) up to 50,4 Gy in 28fx and concomitantly Paclitaxel 50mg/m2 and Carboplatin AUC2 Q1W and Nivolumab as described above. Receives: Drug: Nivolumab; Radiation: Radiotherapy; Drug: Chemotherapy |
| Cohort C | Experimental | Subjects with operable esophageal cancer eligible for neoadjuvant chemoradiotherapy will receive Nivolumab 240mg Q2W, concomitantly with RT Then surgery 4-12 weeks after RT. Within 6-12 months after surgery: Adjuvant Nivolumab 480mg Q4W, for 12 months. 6 patients in total.
Neoadjuvant chemotherapy: Concomitantly Paclitaxel 50mg/m2 and Carboplatin AUC2 Q1W and Radiotherapy: 41,4 Gy in 23 fractions. Receives: Drug: Nivolumab; Radiation: Radiotherapy; Drug: Chemotherapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Safety and Tolerability; Incidence of adverse events using CTCAE 5.0
Measured: From date of treatment allocation until first date of documented disease progression or death assessed during study period or up to at least 100 days after last dose
Secondary outcomes (6)
Response to treatment
Overall Response Rate (RECIST v1.1)
Measured: From date of treatment allocation and during treatment period up to 2 years
Overall Survival
The survival time from date of treatment allocation until first date of documented death
Measured: From date of treatment allocation until first date of documented death assessed up to 5 years after completed treatment
Progression Free Survival
The time from date of treatment allocation until first date of documented disease progression or death whichever comes first
Measured: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Health Related Quality of Life (EQ-5D)
Health Related Quality of Life Measurements, using patients' reported outcomes from EQ-5D
Measured: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Health Related Quality of Life (EORTC QLQ-C30)
Health Related Quality of Life Measurements, using patients' reported outcomes from EORTC QLQ-C30
Measured: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Health Related Quality of Life (EORTC QLQ-OG25)
Health Related Quality of Life Measurements, using patients' reported outcomes from EORTC QLQ-OG25
Measured: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2018
- Study start26 Apr 2018
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Open-label, non-randomized, Parallell Groups, Study of Nivolumab and Radiotherapy in Patients With Esophageal Cancer
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Geir Olav Hjortland, Oslo University Hospital
- Investigators
- Geir O. Hjortland, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03544736
- Sponsor's protocol ID
- CA209-9M9-03
- Status last verified
- Mar 2023
- First submitted
- 25 Apr 2018
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (INEC-study) - a Phase I/II Trial
- ClinicalTrials.gov ID
- NCT03544736
- Acronym / sponsor ID
- CA209-9M9-03
- Conditions
- Esophageal Cancer
- Keywords
- Nivolumab, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 26 Apr 2018 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2040 (estimated)
- First posted
- 4 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer
Detailed description
Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer.
Cohort A: Advanced/inoperable esophageal cancer, eligible for palliative radiotherapy of the primary tumor.
Cohort B: Inoperable esophageal cancer without metastases, eligible for definitive chemoradiotherapy Cohort C: Operable esophageal cancer eligible for neoadjuvant chemoradiotherapy
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Open-label, non-randomized, Parallell Groups, Study of Nivolumab and Radiotherapy in Patients With Esophageal Cancer
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: Nivolumab, Radiation: RadiotherapySubjects having palliative radiotherapy towards esophageal tumor will receive concomitant therapy With Nivolumab i.v. 240mg Q2W: first 6 patients, 360mg Q3W: Next 6 patients or 480mg Q4W: Last 6 patients, treatment to progression or up to 2 years of treatment. Radiotherapy: 2 Gy / day, (5 fx/week) to a total of 20 - 50 Gy in 25fx (2-4Gy/fx) at the decision of the responsible physician. |
| Cohort B | Experimental | Drug: Nivolumab, Radiation: Radiotherapy, Drug: ChemotherapySubjects receiving definitive chemoradiotherapy for esophageal cancer will receive concomitant therapy with Nivolumab 240mg Q2W, during RT, and continued with 480mg Q4W, treatment to progression or up to 1 year after completion of radiotherapy. 6 patients in total. Chemotherapy: Paclitaxel i.v. 175mg/m2 and Carboplatin AUC5, then after 21 days Radiotherapy 1,8 Gy / day (5 fx/week) up to 50,4 Gy in 28fx and concomitantly Paclitaxel 50mg/m2 and Carboplatin AUC2 Q1W and Nivolumab as described above. |
| Cohort C | Experimental | Drug: Nivolumab, Radiation: Radiotherapy, Drug: Chemotherapy, Procedure: SurgerySubjects with operable esophageal cancer eligible for neoadjuvant chemoradiotherapy will receive Nivolumab 240mg Q2W, concomitantly with RT Then surgery 4-12 weeks after RT. Within 6-12 months after surgery: Adjuvant Nivolumab 480mg Q4W, for 12 months. 6 patients in total. Neoadjuvant chemotherapy: Concomitantly Paclitaxel 50mg/m2 and Carboplatin AUC2 Q1W and Radiotherapy: 41,4 Gy in 23 fractions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Three different cohorts of patients with esophageal cancer are studied.
- All of the following conditions must apply to the prospective patient at screening prior to receiving study treatment or any study related procedures (e.g.):
- Age > 18 years
- Patients should have previously untreated histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastroesophageal junction (GEJ), Siewert I, II or III
- Must be ambulatory with a performance status ECOG 0 or 1
Key exclusion criteria (16 listed)
- Previous treatment with radiotherapy towards volumes within the thoracic cavity
- Previous treatment with any PD-1 or PD-L1/2 inhibitor
- Hypersensitivity to the investigational product or any of the drug formula contents
- Esophageal stenting
- T4b if infiltration into the aorta or the trachea
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 |
|---|---|---|
| NivolumabAlso: OpdivoExperimental: Nivolumab | Drug | Cohort A, Cohort B, Cohort C |
| RadiotherapyRadiotherapy | Radiation | Cohort A, Cohort B, Cohort C |
| ChemotherapyAlso: Paclitaxel and CarboplatinChemotherapy | Drug | Cohort B, Cohort C |
| SurgerySurgery | Procedure or surgery | Cohort C |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: From date of treatment allocation until first date of documented disease progression or death assessed during study period or up to at least 100 days after last dose
Safety and Tolerability; Incidence of adverse events using CTCAE 5.0
6 secondary outcomes
Response to treatment
Time frame: From date of treatment allocation and during treatment period up to 2 years
Overall Survival
Time frame: From date of treatment allocation until first date of documented death assessed up to 5 years after completed treatment
Progression Free Survival
Time frame: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Health Related Quality of Life (EQ-5D)
Time frame: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Health Related Quality of Life (EORTC QLQ-C30)
Time frame: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Health Related Quality of Life (EORTC QLQ-OG25)
Time frame: From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
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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.
Geir O. Hjortland principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nivolumab, Radiotherapy and Chemotherapy in people with Esophageal Cancer, run by Oslo University Hospital at 1 site in Norway.
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 25 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 22 Mar 2023. 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 Norway. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of Treatment-Emergent Adverse Events (time frame: From date of treatment allocation until first date of documented disease progression or death assessed during study period or up to at least 100 days after last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Mar 2023.