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

NCT02866383 | Completed Phase 2

• 1 other identifier: GI 1616
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Metastatic Pancreatic Cancer; Metastatic Biliary Tract Cancer

Outcome Measures

Primary Outcomes (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

  6 months

Secondary Outcomes (9)

• Incidence of Treatment-Emergent Adverse Events [Safety]

  12 months

• CBR

  6 months

• Overall response rate (ORR) according to RECIST 1.1

  6 months

• Overall response rate (ORR) according to modified irRC

  6 months

• Progression free survival (PFS) per RECIST 1.1

  6 months

Study Arms (2)

Nivolumab & Radiotherapy

EXPERIMENTAL

Patients 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

Drug: Nivolumab; Radiation: Radiotherapy

Nivolumab & Ipilimumab & Radiotherapy

EXPERIMENTAL

Patients 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

Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiotherapy

Interventions

Nivolumab DRUG

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

Also known as: Opdivo®

Nivolumab & Ipilimumab & Radiotherapy; Nivolumab & Radiotherapy

Ipilimumab DRUG

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)

Also known as: Yervoy®

Nivolumab & Ipilimumab & Radiotherapy

Radiotherapy RADIATION

15 Gy x 1 fraction given on day 1

Nivolumab & Ipilimumab & Radiotherapy; Nivolumab & Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Herlev Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Herlev & Gentofte Hospital

Herlev, 2730, Denmark

Location

Related Publications (2)

• 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.

  PMID: 37744345 DERIVED

• 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.

  PMID: 35476508 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Biliary Tract Neoplasms

Interventions

Nivolumab; Ipilimumab; Radiotherapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• Inna Chen, MD

  Herlev and Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Specialist

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 15, 2016
• Study Start: November 1, 2016
• Primary Completion: January 5, 2022
• Study Completion: November 30, 2022
• Last Updated: September 22, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)