Clinical Trials /

Chemo4METPANC Combination Chemokine Inhibitor, Immunotherapy, and Chemotherapy in Patients With Pancreatic Adenocarcinoma

NCT04543071

Description:

The purpose of this study is to determine if combination treatment with cemiplimab, motixafortide, gemcitabine, and nab-paclitaxel is effective in decreasing the size of the tumor(s), if it will prolong life in patients, and if it's safe. The treatment consists of standard chemotherapy (gemcitabine and nab-paclitaxel) which is FDA approved and is standard treatment for patients with pancreatic adenocarcinoma. Participants will receive immunotherapy (cemiplimab) which activates the body's immune system to attack cancer cells. Cemiplimab is FDA approved for treatment of skin cancer but not for pancreas cancer. Participants will also receive Motixafortide, a new medication which has shown in the laboratory to help immunotherapy work better. Motixafortide has been tested together with immunotherapy (Pembrolizumab), and chemotherapy (5-Fluorouracil and liposomal Irinotecan) and was deemed safe to test additional patients. Motixafortide has not been tested with the specific immunotherapy (Cemiplimab) and chemotherapy (gemcitabine and nab-paclitaxel) which participants will receive and is being tested in this clinical trial.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Chemo4METPANC Combination Chemotherapy in Patients With Pancreatic Adenocarcinoma
  • Official Title: A Phase 2 Study With Combination Chemotherapy (Gemcitabine and Nab-Paclitaxel), Chemokine (C-X-C) Motif Receptor 4 Inhibitor (BL-8040), and Immune Checkpoint Blockade (Cemiplimab) in METastatic Treatment naïve PANCreas Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: AAAS9513
  • NCT ID: NCT04543071

Conditions

  • Pancreatic Cancer
  • Adenocarcinoma of the Pancreas
  • Adenocarcinoma

Interventions

DrugSynonymsArms
Motixafortide (BL-8040)Motixafortide, Cemiplimab, Gemcitabine, Nab-Paclitaxel
CemiplimabMotixafortide, Cemiplimab, Gemcitabine, Nab-Paclitaxel
GemcitabineMotixafortide, Cemiplimab, Gemcitabine, Nab-Paclitaxel
Nab paclitaxelMotixafortide, Cemiplimab, Gemcitabine, Nab-Paclitaxel

Purpose

The purpose of this study is to determine if combination treatment with cemiplimab, motixafortide, gemcitabine, and nab-paclitaxel is effective in decreasing the size of the tumor(s), if it will prolong life in patients, and if it's safe. The treatment consists of standard chemotherapy (gemcitabine and nab-paclitaxel) which is FDA approved and is standard treatment for patients with pancreatic adenocarcinoma. Participants will receive immunotherapy (cemiplimab) which activates the body's immune system to attack cancer cells. Cemiplimab is FDA approved for treatment of skin cancer but not for pancreas cancer. Participants will also receive Motixafortide, a new medication which has shown in the laboratory to help immunotherapy work better. Motixafortide has been tested together with immunotherapy (Pembrolizumab), and chemotherapy (5-Fluorouracil and liposomal Irinotecan) and was deemed safe to test additional patients. Motixafortide has not been tested with the specific immunotherapy (Cemiplimab) and chemotherapy (gemcitabine and nab-paclitaxel) which participants will receive and is being tested in this clinical trial.

Detailed Description

      Pancreas adenocarcinoma (PDAC) is an aggressive pancreatic cancer for which little progress
      has been made towards effective treatment. This is a Phase 2 open-label, multi-center study
      for patients with treatment-naïve metastatic PDAC. The goal of the study is to assess the
      preliminary efficacy of a CXCR4 antagonist (motixafortide), (cemiplimab), gemcitabine and
      nab-paclitaxel compared based on the response rate to historical controls in first line
      metastatic PDAC. Subjects will be treated with 5 days of motixafortide daily alone in the
      priming phase, followed by motixafortide twice a week, cemiplimab once every three weeks and
      and standard of care chemotherapy (gemcitabine and nabpaclitaxel).
    

Trial Arms

NameTypeDescriptionInterventions
Motixafortide, Cemiplimab, Gemcitabine, Nab-PaclitaxelExperimentalParticipants will receive standard FDA-approved doses of gemcitabine and nab-paclitaxel for pancreas cancer and cemiplimab at the dose that is approved for participants with skin cancer. Participants will also receive motixafortide at a dose that has been deemed safe in previous studies when used in combination with immunotherapy and chemotherapy. If the combination study treatment causes a serious side effect in participants, the study treatment will be modified.
  • Motixafortide (BL-8040)
  • Cemiplimab
  • Gemcitabine
  • Nab paclitaxel

Eligibility Criteria

        Inclusion criteria:

          1. Histological or pathological confirmation of metastatic pancreas adenocarcinoma

               1. Cytologic or histologic proof of pancreas adenocarcinoma needs to be verified by
                  the treating institution pathologist, either from the initial diagnostic biopsy
                  or from the required pre-treatment biopsy, prior to initiation of any
                  study-related therapy.

               2. Pathologic confirmation of metastatic (stage IV) disease (unresectable) on
                  research pretreatment biopsy is required prior to initiation of therapy.

               3. Patients with endocrine or acinar pancreatic carcinoma are not eligible for the
                  study.

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          3. Age ≥18 years

          4. Adequate hematological and end-organ function (test results from within 14 days prior
             to initiation of study treatment):

               1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without granulocyte
                  colony-stimulating factor support

               2. White Blood Cell Count (WBC) count ≥ 2.5 x 109 /L (2500/uL)

               3. Lymphocyte count ≥ 0.5 x 109/L (500/uL)

               4. Platelet count ≥ 100 x 109/L (100,000/uL) without transfusion

               5. Hgb ≥ 9.0 g/dL

               6. Aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline
                  phosphatase (ALP) ≤ 2.5X upper limit of normal (ULN), unless elevated secondary
                  to biliary obstruction from the pancreas mass and amenable to decompression prior
                  to initiation of therapy

               7. Serum total bilirubin ≤ 1.5X ULN, unless in patients with known Gilbert disease
                  (≤ 3X ULN), or unless elevated secondary to biliary obstruction from the pancreas
                  mass and amenable to decompression prior to administration of investigational
                  therapy

               8. Albumin ≥ 3.5 g/dL

               9. Creatinine within ULN or calculated creatinine clearance (CrCl) >50 mL/min using
                  the Cockcroft-Gault formula

              10. International normalized ratio (INR) and activated partial thromboplastin time
                  (aPTT) ≤ 1.5X ULN, except for those on stable anticoagulation for at least two
                  weeks

          5. Measurable disease according to Immune Modified (IM)-RECIST and tumor accessible for
             fresh biopsy

          6. Negative pregnancy test: Women of child-bearing potential must have a negative serum
             pregnancy test at screening and must agree to use an effective form of contraception
             from the time of the negative pregnancy test until a minimum of 3 months after the
             last dose of study drug. Effective forms of contraception include abstinence, hormonal
             contraceptive (injectable or implantable) in conjunction with a barrier method. Women
             of non-child-bearing potential must have been postmenopausal for ≥ 1 year or
             surgically sterile.

          7. Birth control agreement: Fertile men must agree to use an effective method of birth
             control with female partners of childbearing potential (condoms plus an additional
             contraceptive method such as an injectable or implantable hormonal contraceptive)
             during the study and for up to 3 months after the last dose of study drug.

          8. Informed consent: Participants must be willing and able to provide written informed
             consent prior to any study-related procedures and to comply with all study
             requirements.

          9. Ability to comply: Participants must be able to comply with the study protocol,
             according to the investigator's judgement.

         10. DVT testing Participants must have undergone lower extremity dopplers to rule out deep
             venous thrombosis (DVT) within the screening period, and undergo therapeutic
             anticoagulation if evidence of DVT is identified.

         11. Anticoagulation treatment Subjects who are stable on full-dose anticoagulation
             medication for at least 2 weeks are considered eligible. However, subjects who have an
             increased clot burden on full-dose anticoagulation, such as central pulmonary
             embolism, or peripheral pulmonary embolism, and DVT within the extremities will be
             considered eligible only with the approval of the Principal Investigator.

        Exclusion criteria:

          1. Prior systemic therapy for PDAC: Participants may not have had systemic chemotherapy,
             investigational therapy, or treatment with T-cell co-stimulating or immune check point
             blockade therapies (including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic
             antibodies) prior to initiation of study treatment.

          2. Prior radiation therapy for PDAC Participants may not have had radiation therapy to
             within two weeks prior to initiation of study treatment. Participants may not have had
             previous radiotherapy to the primary pancreas lesion or a metastatic site except for
             palliation for pain. Participants who receive radiation to 25% or more of the bone
             marrow will be excluded.

          3. Prior surgery for PDAC Participants may not have had surgical resection of PDAC prior
             to initiation of study treatment

          4. Patients currently receiving any other investigational agents

          5. Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1 or
             better, with the exception of alopecia of any grade and Grade ≤ 2 peripheral
             neuropathy

          6. Concomitant treatment with other anti-neoplastic agents (hormone therapy acceptable)

          7. Uncontrolled pleural effusion, pericardial effusion, or ascites. Subjects who required
             drainage within the four weeks prior or require pleural, pericardial, or peritoneal
             catheters for drainage are ineligible.

          8. Uncontrolled tumor-related pain Patients requiring narcotic pain medication must be on
             a stable regimen for at least two weeks prior to study entry.

          9. History of leptomeningeal or brain/ Central Nervous System (CNS) metastases

         10. Uncontrolled hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL, or
             corrected serum calcium > upper limit of normal) or symptomatic hypercalcemia
             requiring continued use of bisphosphonate therapy.

         11. Recent major surgery or significant traumatic injury Participants may not have
             undergone major surgery or experienced significant traumatic injury within 14 days
             prior to initiating study treatment, or be recovering from procedure related adverse
             events of > Grade 1.

         12. Active or history of autoimmune disease or immune deficiency Includes, but is not
             limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
             antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré
             syndrome, or multiple sclerosis, with the following exceptions:

               1. Patients with a history of autoimmune-related hypothyroidism who are on stable
                  thyroid-replacement hormone for the past three months are eligible for the study.

               2. Patients with controlled Type 1 diabetes mellitus who are on a stable insulin
                  regimen for the past month are eligible for the study.

               3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis are
                  excluded) are eligible for the study provided all of following conditions are
                  met:

                    -  Rash must cover <10% of body surface area;

                    -  Disease is well-controlled at baseline and requires only low-potency topical
                       corticosteroids;

                    -  No occurrence of acute exacerbations of the underlying condition requiring
                       psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
                       agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids
                       within the previous 12 months.

         13. History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing
             pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic
             pneumonitis, or evidence of active pneumonitis on screening chest computed tomography
             scan (history of radiation pneumonitis or fibrosis in the radiation field is
             permitted).

         14. Positive for HIV at screening or any time prior to screening Patients without prior
             positive HIV test result will undergo an HIV test at screening, unless not permitted
             under local regulations.

         15. Hepatitis B virus (HBV) infection (chronic or acute) Defined as having a positive
             hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or
             resolved HBV infection, defined as having a negative HBsAg test and a positive total
             hepatitis B core antibody test at screening, are eligible for the study.

         16. Active hepatitis C virus (HCV) infection: Defined as positive HCV antibody test
             followed by a positive HCV RNA test at screening.

             The HCV RNA test will be performed only for patients who have a positive HCV antibody
             test.

         17. Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis,
             fatty liver disease, and inherited liver disease.

         18. Active tuberculosis

         19. Infection: Patients may not have had a severe infection requiring antibiotic treatment
             within the two weeks prior to initiation of study treatment. This includes, but is not
             limited to, hospitalization for complications of infection, bacteremia, or severe
             pneumonia. However, patients who were admitted for biliary tract infection due to bile
             duct obstruction at time of diagnosis must have a functioning biliary stent (as
             evidenced by declining total bilirubin and ≤ 2X ULN) and resolved infection (defined
             by normalization of elevated white blood cell count, absence of signs of infection)
             and completion of an antibiotic course (at least a seven-day course) prior to
             initiation of therapy. Patients receiving prophylactic antibiotics (e.g., to prevent a
             urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
             eligible for the study.

         20. Significant cardiovascular disease: Patient may not have significant cardiovascular
             disease (such as New York Heart Association Class II or greater cardiac disease,
             myocardial infarction, or cerebrovascular accident) within 12 months prior to
             initiation of study treatment, seizure disorder, uncontrolled hypertension, or
             unstable arrhythmia or unstable angina within 3 months prior to initiation of study
             treatment.

         21. Left ventricular ejection fraction below institutional lower limit of normal or below
             50%, whichever is lower.

         22. Baseline QTcF ≥ 450 ms (males) or ≥ 470 ms (females)

         23. Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study
             treatment

         24. Prior autologous stem cell, allogeneic stem cell, or solid organ transplantation

         25. History of other malignancy Patient may not have a history of malignancy other than
             PDAC within two years prior to screening, with the exception of those with a
             negligible risk of metastasis or death (e.g., 5- year overall survival of > 90%), such
             as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
             localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.

         26. Recent vaccination: Patients may not have been treated with a live, attenuated vaccine
             within four weeks prior to initiation of study treatment, or anticipate the need for
             such a vaccine during treatment with cemiplimab or within five months after the last
             dose of cemiplimab.

         27. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins

         28. Known allergy or hypersensitivity to any of the study drug excipients

         29. Recent immunosuppressive treatment: Patients may not have been treated with systemic
             immunosuppressive medication (including, but not limited to, corticosteroids,
             cyclophosphamide, azathioprine, methotrexate, thalidomide, calcineurin inhibitors, and
             anti-tumor necrosis factor alpha agents) within two weeks prior to initiation of study
             treatment, or anticipate the need for systemic immunosuppressive medication during the
             course of the study, with the following exceptions:

             a. Patients who received a one-time pulse dose of systemic immunosuppressant
             medication are eligible for the study after approval from the Principal Investigator.

         30. Pregnancy: Pregnant women are excluded from this study because there is an unknown,
             but potential risk for adverse events to the fetus. Breastfeeding should be
             discontinued prior to start of treatment because there is an unknown, but potential
             risk for adverse events in nursing infants secondary to treatment.

         31. Other contraindicated conditions Any other disease, metabolic dysfunction, physical
             examination finding, or clinical laboratory finding that contraindicates the use of an
             investigational drug, may affect the interpretation of the results, or may render the
             patient at high risk from treatment complications in the opinion of the treating
             investigator.

         32. Uncontrolled psoriasis, porphyria, proximal myopathy or neuropathy

         33. Severe depression Subjects hospitalized for depression within the past two years, or
             who have prior suicidal attempts will be excluded.

         34. Has received transfusions of blood products (including platelets or red blood cells)
             within 4 weeks prior to study Day 1.

         35. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for
             chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for
             orthostatic hypotension or adrenal insufficiency are eligible for the study if
             receiving equivalent to ≤ 10 mg of prednisone daily (10mg prednisone is equivalent to
             either cortisone - 50mg; hydrocortisone - 40mg; triamcinolone - 8mg; prednisolone -
             10mg; methylprednisolone - 8mg; betamethasone - 1.5mg; or dexamethasone - 1.5mg).
             Patients receiving > 10 mg of prednisone or equivalent per day for greater than five
             days within 28 days of starting study related therapy are not eligible. Steroids
             administered prior to gemcitabine and nab-paclitaxel should be administered as per
             standard institutional guidelines.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (Complete Response (CR) + Partial Response (PR))
Time Frame:16 weeks
Safety Issue:
Description:Complete response is defined as the disappearance of all lesions. Partial response is defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.

Secondary Outcome Measures

Measure:Incidence of Treatment Related Toxicities
Time Frame:Up to 5 years
Safety Issue:
Description:All participants will be evaluable for toxicity from the time of their first treatment with the study drugs. The counts of treatment-related toxicities will be reported by type and severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.
Measure:Median Overall Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Overall survival is defined as the time from the date of first treatment with study drug to the time of death from any cause or last follow-up if alive.
Measure:Median Progression Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Progression free survival is defined as the time from first treatment with the study drug to the earliest of either disease progression or death from any cause.
Measure:Duration of Clinical Benefit
Time Frame:Up to 5 years
Safety Issue:
Description:Duration of clinical benefit is defined as the time from first treatment with the study drug to the earliest of either disease progression or death from any cause in subjects who achieved a CR, PR, or stable disease (SD).
Measure:Disease Control Rate
Time Frame:16 weeks
Safety Issue:
Description:The number of participants that achieve disease control rate (CR+PR+SD) by 16 weeks.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Gulam Manji

Last Updated

September 8, 2020