Clinical Trials /

Study of Talimogene Laherparepvec (T-VEC) in Pancreatic Cancer

NCT03086642

Description:

The purpose of this study is to find out which doses of talimogene laherparepvec (T-Vec) can be given safely to participants with pancreatic cancer that is either too big to be taken out by surgery or has spread to other parts of the body. The study will also see if T-Vec can cause tumor shrinkage or prevent its growth. The primary objective is to determine the rate of dose limiting toxicity at tested doses of talimogene laherparepvec administered endoscopically to pancreatic tumors, and to identify a maximum tolerated dose (MTD). Secondary exploratory efficacy endpoints include change in longest diameter in the injected lesion(s), overall response rate (ORR) per RECIST v1.1 and modified immune-related response criteria (mirRC as defined in section 11), progression free survival (PFS) and overall survival (OS) at 6, 12, and 24 months.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Talimogene Laherparepvec (T-VEC) in Pancreatic Cancer
  • Official Title: Study of Talimogene Laherparepvec Administered Endoscopically for the Treatment of Locally Advanced or Metastatic Pancreas Cancer Refractory to at Least One Chemotherapy Regimen

Clinical Trial IDs

  • ORG STUDY ID: AAAQ9966
  • NCT ID: NCT03086642

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
Talimogene laherparepvecT-Vec, T VecT-Vec

Purpose

The purpose of this study is to find out which doses of talimogene laherparepvec (T-Vec) can be given safely to participants with pancreatic cancer that is either too big to be taken out by surgery or has spread to other parts of the body. The study will also see if T-Vec can cause tumor shrinkage or prevent its growth. The primary objective is to determine the rate of dose limiting toxicity at tested doses of talimogene laherparepvec administered endoscopically to pancreatic tumors, and to identify a maximum tolerated dose (MTD). Secondary exploratory efficacy endpoints include change in longest diameter in the injected lesion(s), overall response rate (ORR) per RECIST v1.1 and modified immune-related response criteria (mirRC as defined in section 11), progression free survival (PFS) and overall survival (OS) at 6, 12, and 24 months.

Detailed Description

      Pancreatic ductal adenocarcinoma (PDA) is an area of great unmet need. PDA accounts for 90%
      of pancreatic tumors in 2016. The standard of care for pancreas cancer is cytotoxic
      chemotherapy, but this is not particularly effective with best response rates reported of
      20-30% and no significant long-term 5-year survival for patients who are not surgical
      candidates. Talimogene laherparepvec (previously known as OncoVEXGM-CSF) is an intratumorally
      delivered oncolytic immunotherapy comprised of an immune-enhanced herpes simplex virus type-1
      (HSV-1) that selectively replicates in solid tumors. Talimogene laherparepvec was the first
      oncolytic viral therapy to be approved by the Federal Drug Administration (FDA) for the
      treatment of cancer, specifically melanoma. There is the potential that talimogene
      laherparepvec could exert a systemic effect mitigating the potential of PDA to metastasize.

      This is a phase 1 dose escalation study to evaluate the safety of talimogene laherparepvec in
      PDA. To find out which doses are safe, all participants enrolled in this study will receive
      up to 4 injections of T-Vec. At least two doses will be evaluated in this study, depending on
      how many side effects are seen at each dose. Participants will not be able to pick the dose,
      as this will be determined based on the study experience with participants enrolled
      previously.
    

Trial Arms

NameTypeDescriptionInterventions
T-VecExperimentalAll enrolled patients will receive a test dose of talimogene laherparepvec (10^6 plaque forming units (PFU)/ml) on day 1, followed by treatment doses at escalating concentrations weeks 4, 7, and 10. A biopsy will be obtained during each scheduled endoscopy prior to talimogene laherparepvec injection.
  • Talimogene laherparepvec

Eligibility Criteria

        Inclusion Criteria:

          1. Patient must have pathologically confirmed, locally advanced or metastatic pancreatic
             adenocarcinoma deemed surgically unresectable by a surgeon with expertise in
             pancreatic cancer

          2. Disease must be refractory to or intolerant of at least first-line chemotherapy which
             contains 5-fluorouracil or gemcitabine

          3. The primary lesion must be accessible for endoscopic biopsy and injection as evaluated
             by a gastroenterologist at NewYork Presbyterian -Columbia. Further, the patient must
             be deemed able to tolerate repeated endoscopy procedures by an anesthesiologist and/or
             gastroenterologist at NewYork Presbyterian-Columbia

          4. Age 18 years or older

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

          6. Radiologically measurable injectable disease in the pancreas or surgical bed from
             prior ≥1cm, as defined by RECIST v1.1

          7. Ability to understand and the willingness to sign a written informed consent document

          8. Females of child-bearing potential (defined as a sexually mature woman who (1) has not
             undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy
             [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal
             for at least 24 consecutive months [i.e., has had menses at any time during the
             preceding 24 consecutive months]) must:

             i. Either commit to true abstinence from heterosexual contact (which must be reviewed
             on a monthly basis), or agree to use, and be able to comply with, effective
             contraception (</=1% failure rate annually) without interruption, 28 days prior to
             starting therapy (including dose interruptions), and while on study medication or for
             a period of 30 days following treatment completion. [Periodic abstinence (eg,
             calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
             acceptable methods of contraception].

             ii. Have a negative urine or serum pregnancy test within 72 hours prior to enrollment.
             If urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.This applies even if the subject practices true abstinence from
             heterosexual contact.

          9. Male subjects must practice true abstinence or agree to use a condom during sexual
             contact with a pregnant female or a female of childbearing potential while
             participating in the study, during dose interruptions and for 30 days following
             treatment discontinuation, even if he has undergone a successful vasectomy.

         10. Adequate organ and marrow function as defined below without need for hematopoietic
             growth factor or transfusion support:

               -  Hemoglobin ≥8.0g/dl

               -  Platelets ≥75,000/microliter (mcL)

               -  Absolute neutrophil count (ANC) ≥1500/mm3 (1.5x109/L)

               -  Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) or Direct
                  bilirubin ≤ ULN with total bilirubin >1.5 x ULN

               -  Aspartate aminotransferase (AST) (SGOT)/alanine transaminase (ALT) (SGPT) ≤1.5 x
                  ULN

               -  INR and aPTT ≤ 1.5 x ULN Unless the patient is on therapeutic anticoagulation in
                  which case the international normalized ratio (INR) and activated partial
                  thromboplastin time (aPTT) must be within the therapeutic range of intended use
                  of anti-coagulants

               -  Serum creatinine ≤1.5 x ULN or 24 hour creatinine clearance ≥60 mL/min/1.73 m2 by
                  Cockcroft-Gault

               -  Lipase ≤3 x ULN

        Exclusion Criteria:

          1. Cystic pancreatic cancer. Microcystic disease may be eligible

          2. Patients with pancreatic metastases deemed likely to limit the patient's ability to
             participate in the study for the complete duration (ie. >3 months), including but not
             limited to:

             a. Presence of central nervous system (CNS) metastasis including brain metastasis or
             compromise resulting from extrinsic disease in the bone or dura b. Presence of more
             than 5 liver metastases or one liver metastasis measuring more than 3cm c. Oxygen
             requirement attributable to pleural effusion or other malignant process d. Symptomatic
             ascites or radiographic evidence of more than trace ascites

          3. History of other malignancy within the past 3 years with the following exceptions:

               1. malignancy treated with curative intent and with no known active disease present
                  and has not received chemotherapy for >3 years before randomization and felt to
                  be at low risk for recurrence by the treating physician

               2. adequately treated non-melanoma skin cancer without evidence of disease at the
                  time of randomization • adequately treated cervical carcinoma in situ without
                  evidence of disease at the time of randomization

               3. adequately treated breast ductal carcinoma in situ without evidence of disease at
                  the time of randomization • prostatic intraepithelial neoplasia without evidence
                  of prostate cancer at the time of randomization

               4. adequately treated superficial or in situ carcinoma of the bladder without
                  evidence of disease at the time of randomization

          4. Pancreatitis that is active or within the preceding 3 months which in the judgment of
             the endoscopist would make tumor injection likely to trigger severe recurrent
             pancreatitis.

          5. Prior chemotherapy or radiotherapy within 14 days prior to first dose of therapy or
             has not recovered to CTCAE grade 1 or better from adverse event at time of enrollment
             due to cancer therapy administered more than 28 days prior to enrollment. or prior
             biological cancer therapy, targeted therapy, or major surgery within 28 days prior to
             first dose of therapy or unresolved grade 2 or greater toxicity from prior treatment,
             including chemotherapy, hormonal therapy, or radiotherapy, at the time of study
             enrollment. The following ongoing treatments are permitted:

               1. Hormone-replacement therapy or oral contraceptives

               2. Hormone therapy for primary prevention of breast cancer

        5. Patients may not receive Coumadin while on study. Patients may receive low molecular
        weight heparin or novel oral anticoagulants (eg. dabigatran, apixaban, rivaroxaban)
        provided that the dose is held 1-2 days before injections are given and biopsies are
        performed per the protocol. Anti-platelet agents and herbal substances are allowed at the
        discretion of the treating endoscopist.

        6. Radiation to the abdominal area within 28 days of first dose of therapy or prior
        radiotherapy in which the field does not overlap the injection sites or
        non-immunosuppressive targeted therapy within 14 days prior to enrollment or has not
        recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered
        more than 14 days prior to enrollment. .

        7. The patient has not recovered to CTCAE grade 1 or better from adverse event at time of
        enrollment due to cancer therapy administered more than 28 days prior to enrollment

        8. Prior biological cancer therapy, targeted therapy, or major surgery within 28 days prior
        to first dose of therapy or major surgery within 28 days prior to enrollment or has not
        recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered
        more than 28 days prior to enrollment. Adjuvant hormonal therapy is allowed..

        9. Unresolved grade 2 or greater toxicity from most recent treatment, including
        chemotherapy, hormonal therapy, or radiotherapy, at the time of study enrollment.

        10. The following ongoing treatments are permitted:

          1. Hormone-replacement therapy or oral contraceptives

          2. Hormone therapy for primary prevention of breast cancer

             11. Patients may not receive Coumadin while on study. Patients may receive low
             molecular weight heparin or novel oral anticoagulants (eg. dabigatran, apixiban,
             rivaroxaban) provided that the dose is held 1-2 days before injections are given and
             biopsies are performed per the protocol. Anti-platelet agents and herbal substances
             are allowed at the discretion of the treating endoscopist.

             12. Active herpetic skin lesions or prior complications of herpetic infection (e.g.,
             herpetic keratitis or encephalitis) or requires intermittent or chronic systemic
             (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other
             than intermittent topical use.

             13. Previous treatment with talimogene laherparepvec or any other oncolytic virus

             14. Prior therapy with tumor vaccine

             15. Received live vaccine within 28 days of tumor enrollment

             16. Currently receiving treatment with another investigational device or drug study,
             or < 28 days since ending treatment with another investigational device or drug
             study(s). Other investigational procedures while participating in this study are
             excluded

             17. Known to have acute or chronic active hepatitis B infection, hepatitis C
             infection, or known to have human immunodeficiency virus (HIV) infection.

             18. Subject has known sensitivity to talimogene laherparepvec or any of its components
             to be administered during dosing.

             19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection including Tuberculosis (TB) and C. difficile, symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements. This includes known
             clinically significant liver disease, including active viral, alcoholic, or other
             hepatitis; cirrhosis; fatty liver; and inherited liver disease

             20. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not
             limited to hospitalization for complications of infection, bacteremia, or severe
             pneumonia

             21. Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of
             need for a major surgical procedure during the course of the study

             22. Female subject of childbearing potential who is unwilling to use acceptable
             method(s) of effective contraception during study treatment and through 3 months after
             the last dose of talimogene laherparepvec. (Note: Women not of childbearing potential
             are defined as: Any female who is post-menopausal [age > 55 years with cessation of
             menses for 12 or more months or less than 55 years but not spontaneous menses for at
             least 2 years or less than 55 years and spontaneous menses within the past 1 year, but
             currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with
             postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating
             hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according
             to the definition of "postmenopausal range" for the laboratory involved] or who have
             had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).

             23. Sexually active subjects and their partners unwilling to use male or female latex
             condom to avoid potential viral transmission during sexual contact while on treatment
             and within 30 days after treatment with talimogene laherparepvec.

             24. Nursing patients are not allowed on the study and women must commit to no
             lactation during the course of the study.

             25. Subject who is unwilling to minimize exposure with his/her blood or other body
             fluids to individuals who are at higher risks for HSV-1 induced complications such as
             immunosuppressed individuals, individuals known to have HIV infection, pregnant women,
             or children under the age of 1 year, during talimogene laherparepvec treatment and
             through 30 days after the last dose of talimogene laherparepvec.

             Immunotherapy-Related Exclusion Criteria:

             26. History or evidence of active autoimmune disease that requires systemic treatment
             (ie, with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment for patients with prior allogeneic bone marrow
             transplantation or prior solid organ transplantation.

               -  The use of inhaled or oral corticosteroids and mineralocorticoids (e.g.,
                  fludrocortisone) for patients with orthostatic hypotension or adrenocortical
                  insufficiency is allowed.

                  27. Received live vaccine within 28 days prior to enrollment.

                  28. Evidence of clinically significant immunosuppression such as the following:

               -  Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

               -  HIV positive

               -  Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
                  doses > 10 mg/day of prednisone or equivalent within 2 months prior to enrollment

               -  Concurrent opportunistic infection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:36-48 months
Safety Issue:
Description:To determine the highest dose of study treatment that does not cause unacceptable side effects.

Secondary Outcome Measures

Measure:Change in size of injected lesion(s)
Time Frame:baseline, 11 weeks
Safety Issue:
Description:To make an exploratory assessment of activity of talimogene laherparepvec in pancreatic cancer, as measured by change in size of the injected lesion(s)
Measure:Overall response rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:The percentage of patients whose cancer shrinks or disappears after treatment.
Measure:Progression-free survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:The length of time during and after the study treatment of cancer, that a patient lives with the disease but it does not get worse.
Measure:Overall survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:The length of time from either the date of diagnosis or the start of study treatment for cancer, that patients diagnosed with the disease are still alive.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yvonne Saenger

Trial Keywords

  • locally advanced pancreatic cancer
  • locally advanced pancreas cancer
  • metastatic pancreatic cancer
  • metastatic pancreas cancer
  • refractory
  • refractory pancreatic cancer
  • refractory pancreas cancer
  • T-Vec
  • T Vec

Last Updated

November 13, 2019