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Metastatic Pancreatic CancerPhase 2CheckPACNCT02866383

Immune Checkpoint Inhibition in Combination With Radiation Therapy in Pancreatic Cancer or Biliary Tract Cancer Patients

A Phase 2 study testing Nivolumab, Ipilimumab and Radiotherapy in people with Metastatic Pancreatic Cancer and Metastatic Biliary Tract Cancer, run by Herlev Hospital at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, randomized, open-label phase 2 study in patients with metastatic PC or BTC refractory or intolerant to at least one line of prior systemic chemotherapy with gemcitabine or platinum-containing regimens to determine the efficacy and safety of nivolumab or nivolumab plus ipilimumab administered… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Ipilimumab and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
1 siteDenmark
Study dates
Nov 2016to 30 Nov 2022
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Signed informed consent
  • Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
  • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
  • Histopathological confirmation of pancreatic adenocarcinoma or BTC prior to entering this study OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are consistent with a diagnosis of PC or BTC
  • At least one measurable primary in-situ (or locally-recurrent) or metastatic tumor must be present and, in the opinion of radiation oncologist, be amenable to RT as planned in the protocol and at least one additional metastatic tumor that will not undergo RT and which is measurable according to RECIST 1.1 criteria. Both lesions must be accessible for image-guided percutaneous biopsy
  • There is no upper limit on the number of prior chemotherapy regimens received. Patients must have received and failed or intolerance to at least one line of prior systemic chemotherapy with gemcitabine or platinum-containing regimens for unresectable and/or metastatic PC or BTC
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  • Age > 18 years and older
  • Life expectancy greater than 3 months
  • ECOG/WHO Performance Status (PS) 0-1
  • Patients must have normal organ and marrow function as defined below:
  • White blood cell count (WBC) ≥ 2 x 10⁹/L
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
  • Hemoglobin ≥ 5,6 mmol/l
  • Platelet count ≥ 100 x 10⁹/L
  • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin < 3.0 mg/dL)
  • ASAT/ALAT ≤ 3 x ULN ( < 5 x ULN if known liver metastasis)
  • PP ≥ 40 or INR ≤ 1.5
  • Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 40 mL/min (using the Cockcroft-Gault formula)
  • Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated per protocol. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. WOCBP should therefore use an 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.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
  • Women must not be breastfeeding
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year The investigator shall review contraception methods and the time period that contraception must be followed. Men that are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. Men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half lives) after the last dose of investigational drug. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception
  • Subjects must have signed and dated a BIOPAC IRB/IEC approved written informed consent form and patients with BTC must have signed and dated a CHOCA in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care

Who cannot join

  • Malignant ascites that is clinically detectable by physical examination or is symptomatic. Evidence of radiographic ascites that is not clinically significant will not be exclusion criteria
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • No chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
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  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab- and ipilimumab containing regimen
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Allergies and Adverse Drug Reaction
  • History of allergy to study drug components
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • WOCBP who are pregnant or breastfeeding
  • Women with a positive pregnancy test at enrollment or prior to administration of study medication
  • Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Herlev & Gentofte Hospital

    Herlev, 2730

Other trials in Denmark

About this study

Official title: A Prospective Randomized, Open-label Phase 2 Study of Immune Checkpoint Inhibition, Nivolumab With or Without Ipilimumab in Combination With Radiation Therapy in Pretreated Patients With Metastatic Pancreatic Cancer or Biliary Tract Cancer.

This is a prospective, randomized, open-label phase 2 study in patients with metastatic PC or BTC refractory or intolerant to at least one line of prior systemic chemotherapy with gemcitabine or platinum-containing regimens to determine the efficacy and safety of nivolumab or nivolumab plus ipilimumab administered concurrently with high dose RT. Patients with metastatic PC or BTC who are feasible candidates for radiation and biopsy of primary and/or metastatic lesions will be included.

Read the detailed description

This was a randomized phase II trial conducted at Herlev \& Gentofte Hospital. Patients were stratified according to PS and randomized into two arms (1:1) (Appendix Figure A1 and Data Supplement, online only). Patients received SBRT consisting of 15 Gy (day 1) to a single primary or metastatic lesion with 3 mg/kg of intravenous nivolumab (IV) on day 1 and every 2 weeks (q2w) (Arm A), or SBRT consisting of 15 Gy (day 1) with 3 mg/kg of IV nivolumab (day 1) q2w and 1 mg/kg of IV ipilimumab on day 1 and every 6 weeks (Arm B).

A safety phase involving a run-in assessment of three patients from each arm (n = 6) was followed by the expansion phase. The patients were monitored for dose-limiting toxicities prior to the expansion. Treatment was continued for a maximum of 52 weeks or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or clear clinical deterioration according to the investigator's judgment.

Being tested
Nivolumab, Ipilimumab, Radiotherapy
Medical subject headings
Pancreatic Neoplasms, Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo®

    3 mg/kg is given over 60 minutes I.V. on day 1 just after radiation and then every 2 weeks (q2w)

  • IpilimumabDrug

    Also called Yervoy®

    1 mg/kg is given over 90 minutes I.V. on day 1 30 minutes after the completion of nivolumab infusion and then every 6 weeks IV (q6w)

  • RadiotherapyRadiation

    15 Gy x 1 fraction given on day 1

Study groups in NCT02866383
Study groupRoleWhat they receive
Nivolumab & RadiotherapyExperimentalPatients will receive nivolumab 3 mg/kg over 60 minutes as an IV infusion on day 1 just after RT and then every 2 weeks (q2w), for a maximum of 52 weeks
Receives: Drug: Nivolumab; Radiation: Radiotherapy
Nivolumab & Ipilimumab & RadiotherapyExperimentalPatients will receive nivolumab 3 mg/kg over 60 minutes as an IV infusion on day 1 just after RT. Thirty minutes after the completion of nivolumab infusion patients will receive ipilimumab 1 mg/kg over 90 minutes IV as an IV infusion. Nivolumab will be given every 2 weeks (q2w) and ipilimumab every 6 weeks (q6w), respectively for a maximum of 52 weeks
Receives: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical benefit rate (CBR)

    Stable disease (SD) or complete response (CR) or partial response (PR)according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    Measured: 6 months

Secondary outcomes (9)

  1. Incidence of Treatment-Emergent Adverse Events [Safety]

    Assessment based on AEs, SAEs, laboratory abnormalities

    Measured: 12 months

  2. CBR

    CBR according to modified immune-related Response Criteria (irRC)

    Measured: 6 months

  3. Overall response rate (ORR) according to RECIST 1.1

    PR or CR according to RECIST 1.1

    Measured: 6 months

  4. Overall response rate (ORR) according to modified irRC

    PR or CR according to modified irRC

    Measured: 6 months

  5. Progression free survival (PFS) per RECIST 1.1

    Time from the date of randomization until the date of PD determined by investigator assessment of objective radiographic disease assessments per RECIST 1.1, or death due to any cause if sooner

    Measured: 6 months

  6. Progression free survival (PFS) per modified irRC

    Time from the date of randomization until the date of PD determined by investigator assessment of objective radiographic disease assessments per modified irRC, or death due to any cause if sooner

    Measured: 6 months

  7. Overall survival (OS) probability at 6 months

    The Kaplan-Meier estimate of proportion of patients that survived from the date of randomization by 6 months

    Measured: 6 months

  8. OS

    Time from the date of randomization until death due to any cause

    Measured: 12 months

  9. QoL

    Quality of Life Questionnaire C30 Version 3.0

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2016 (estimated)
  2. Study startNov 2016
  3. Primary completion5 Jan 2022
  4. Study completion30 Nov 2022

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02866383
Sponsor's protocol ID
GI 1616
Acronym
CheckPAC
Status last verified
Sep 2023
First submitted
8 Aug 2016
Last updated
22 Sep 2023
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Kjaer LK, Theile S, Madsen K, Johansen JS, Holmstrom MO, Andersen MH, Chen IM. Impact of Liver Metastases on Outcomes With Chemotherapy or Immune Checkpoint Inhibitors in Pancreatic Cancer. Immun Inflamm Dis. 2026 Oct;14(10):e70545. doi: 10.1002/iid3.70545.

    PubMed 42836590

  • Johansen AZ, Novitski SI, Hjaltelin JX, Theile S, Boisen MK, Brunak S, Madsen DH, Nielsen DL, Chen IM. Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy. Front Immunol. 2023 Sep 7;14:1228907. doi: 10.3389/fimmu.2023.1228907. eCollection 2023.

    PubMed 37744345

  • Chen IM, Johansen JS, Theile S, Hjaltelin JX, Novitski SI, Brunak S, Hasselby JP, Willemoe GL, Lorentzen T, Madsen K, Jensen BV, Wilken EE, Geertsen P, Behrens C, Nolsoe C, Hermann KL, Svane IM, Nielsen D. Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC). J Clin Oncol. 2022 Sep 20;40(27):3180-3189. doi: 10.1200/JCO.21.02511. Epub 2022 Apr 27.

    PubMed 35476508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and Radiotherapy in people with Metastatic Pancreatic Cancer and Metastatic Biliary Tract Cancer, run by Herlev Hospital at 1 site in Denmark.

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 23 inclusion and 15 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 22 Sep 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 Denmark. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Clinical benefit rate (CBR) (time frame: 6 months). 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 NCT02866383, which also lists 3 linked publications.

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 Sep 2023.

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