Clinical Trials /

A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6)

NCT02576665

Description:

The purpose of this trial is to evaluate changes in immune activity relative to baseline following treatment with Toca 511 and Toca FC in patients with solid tumors (including recurrent high grade glioma [rHGG]) or lymphoma. This is a multicenter, open-label study of Toca 511 and Toca FC. Patients with advanced solid tumors or lymphoma, for whom curative options are not available, will be enrolled into the study, subject to all entry criteria. Tumors must be accessible to biopsy and/or resection. Patients will be qualified based on the presence of specific molecular characteristics, documented by Foundation Medicine (or equivalent) genomic profile report, and specific tumor types. Toca 511 will be administered by IV injection followed by (1) intratumoral injection following biopsy or (2) injection into the resection cavity wall following planned resection in the case of rHGG or brain metastases. Toca FC will be administered orally in cycles of therapy. Patients not undergoing resection of brain tumors will undergo 2 biopsies to allow assessment of baseline and follow-up immune activity in the tumor. Changes in immune activity in peripheral blood will be measured in all patients.

Related Conditions:
  • Anaplastic Astrocytoma
  • Bladder Carcinoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Glioblastoma
  • Head and Neck Carcinoma
  • Lymphoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6)
  • Official Title: A Phase 1b Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: Tg 511-15-02
  • NCT ID: NCT02576665

Conditions

  • Colorectal Cancer
  • Triple Negative Breast Cancer
  • Pancreatic Cancer
  • Non-Small Cell Lung Cancer
  • Head and Neck Cancer
  • Ovarian Cancer
  • Lymphoma
  • Sarcoma
  • Bladder Cancer
  • Melanoma
  • IDH1 Mutated Solid Tumors
  • IDH1 Mutated or MGMT Methylated Recurrent High Grade Glioma

Interventions

DrugSynonymsArms
Toca 511vocimagene amiretrorepvec, RRV, retroviral replicating viralToca 511/Toca FC
Toca FCFlucytosine, 5-FC, 5-FluorocytosineToca 511/Toca FC

Purpose

The purpose of this trial is to evaluate changes in immune activity relative to baseline following treatment with Toca 511 and Toca FC in patients with solid tumors (including recurrent high grade glioma [rHGG]) or lymphoma. This is a multicenter, open-label study of Toca 511 and Toca FC. Patients with advanced solid tumors or lymphoma, for whom curative options are not available, will be enrolled into the study, subject to all entry criteria. Tumors must be accessible to biopsy and/or resection. Patients will be qualified based on the presence of specific molecular characteristics, documented by Foundation Medicine (or equivalent) genomic profile report, and specific tumor types. Toca 511 will be administered by IV injection followed by (1) intratumoral injection following biopsy or (2) injection into the resection cavity wall following planned resection in the case of rHGG or brain metastases. Toca FC will be administered orally in cycles of therapy. Patients not undergoing resection of brain tumors will undergo 2 biopsies to allow assessment of baseline and follow-up immune activity in the tumor. Changes in immune activity in peripheral blood will be measured in all patients.

Trial Arms

NameTypeDescriptionInterventions
Toca 511/Toca FCExperimentalToca 511: 14 mL intravenously daily for 3 days followed by up to 4 mL intratumorally or into resection cavity walls following biopsy or resection. Cutaneous melanoma patients may receive intralesional injections (up to 4 mL) daily for 5 days. Toca FC: 220 mg/kg/day orally starting at Week 5-6. Cycles are 5- to 7- day courses of treatment every 4 to 6 weeks.
  • Toca FC

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has given written informed consent.

          2. Patient is between 18 and 75 years of age, inclusive.

          3. Patient has an advanced malignancy that has progressed or recurred following standard
             therapy for advanced disease, and for which no curative therapies are available.

          4. Patient has histologically confirmed (1) colorectal cancer, triple negative breast
             cancer, pancreatic cancer, non-small cell lung cancer, head and neck cancer, ovarian
             cancer, lymphoma, sarcoma, bladder cancer, or melanoma with defects in one or more of
             the following genes: ABL2, ACVR1B, APC, ASXL1, ATM, ATR, BLM, BRCA1, BRCA2, CDK12,
             CDKN1A, CDKN1B, CDKN2A, CHD4, CYLD, DICER1, DNMT3A, ERBB3, EZH2, FGFR2, FLT3, GATA3,
             HGF, KDM6A, KDR, KEAP1, KIT, KMT2D, KRAS, MAGI2, MAP3K1, MED12, MET, MSH-2, MSH-6,
             MYC, NA, NF1, NF2, NOTCH1, NOTCH2, NRAS, NSD1, PIK3C2B, PIK3CA, PIK3CB, PIK3R1, PTCH1,
             PTPN11, RB1, RUNX1, SETD2, SMARCA4, SOX9, STAG2, TAF1, TBX3, TET2, TP53, XPO1; (2)
             documented IDH1 mutated solid tumor (other than glioma); or (3) documented IDH1
             mutated or MGMT promoter methylation positive glioblastoma multiforme (GBM) or
             anaplastic astrocytoma. Note: Genetic abnormalities must be documented by Foundation
             Medicine (or equivalent) genomic profile report.

          5. Patient has an estimated life expectancy of at least 6 months.

          6. Patient has adequate organ function, as indicated by the following laboratory values

               -  Bone marrow: hemoglobin ≥ 10 g/dL, platelet count ≥ 100,000/mm3, absolute
                  neutrophil count ≥ 1,500/ mm3, absolute lymphocyte count ≥ 500/ mm3.

               -  Liver: total bilirubin ≤ 1.5 x the upper limit of normal (ULN; unless known
                  Gilbert's syndrome); alanine aminotransferase ≤ 2.5 x ULN (≤ 5.0 x ULN in
                  patients with liver metastases).

               -  Kidney: estimated glomerular filtration rate (Cockcroft-Gault) ≥ 50 mL/min.

          7. Women of childbearing potential (defined as not postmenopausal [ie, ≥ 12 months of
             non-therapy-induced amenorrhea] or not surgically sterile) must have a negative serum
             pregnancy test within 21 days prior to initiation of Toca 511, and be willing to use
             an effective means of contraception in addition to barrier methods (condoms).

          8. Patient and partner are willing to use condoms for 12 months after receiving Toca 511
             or until there is no evidence of the virus in his/her blood, whichever is longer.

          9. Patients with solid tumors or lymphoma must have 1 or more tumors accessible to biopsy
             or resection, including biopsy allowing multiple cores from at least 1 lesion (fine
             needle aspiration is excluded), incisional or excisional biopsy, and/or resection.
             Note: Patients with resectable brain metastases must be undergoing planned resection.
             Patients with rHGG must be undergoing planned subtotal or gross total resection.

         10. Patient has a tumor amenable to injection of Toca 511 (ie, ≥ 2 cm and not close to or
             invading major vessels).

         11. Patient has an ECOG Performance Status score of 0 or 1 (solid tumors) or KPS score ≥
             70 (rHGG).

         12. Patient has measurable disease by RECIST version 1.1 (solid tumors) or Lugano
             (lymphoma) criteria or evaluable or measureable disease by Macdonald criteria (rHGG).

         13. Patients with GBM or anaplastic astrocytoma must be at first or second recurrence
             (including this recurrence) or have progressed following initial definitive multimodal
             therapy with surgery, temozolomide, and radiation (confirmed by diagnostic biopsy with
             local pathology review or contrast-enhanced magnetic resonance imaging [MRI]). If
             first recurrence is documented by MRI, an interval of at least 12 weeks after the end
             of prior radiation therapy is required, unless there is either histopathologic
             confirmation of recurrent tumor or new enhancement on MRI outside the radiotherapy
             treatment field.

        Exclusion Criteria:

          1. Patient has a history of other malignancy, unless the patient has been disease free
             for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin
             cancer is acceptable regardless of time, as well as localized prostate carcinoma or
             cervical carcinoma in situ, after curative treatment.

          2. Patient has or had any active infection requiring antibiotic, antifungal, or antiviral
             therapy within the 2 weeks prior to administration of Toca 511.

          3. Patient received chemotherapy within 2 weeks prior to initiation of treatment with
             Toca 511 (6 weeks for nitrosoureas).

          4. Patient received investigational treatment within 2 weeks or immunotherapy or antibody
             therapy within 28 days prior to initiation of treatment with Toca 511, and/or has not
             recovered from toxicities associated with such treatment.

          5. For patients with rHGG, the patient intends to undergo treatment with the Gliadel®
             wafer at the time of planned resection (ie, on-study surgery) or has received the
             Gliadel wafer < 30 days from the date of planned resection.

          6. Patient has any bleeding diathesis, or must take anticoagulants or antiplatelet
             agents, including nonsteroidal anti inflammatory drugs, that cannot be stopped for
             biopsy or surgery.

          7. Patient has severe pulmonary, cardiac, or other systemic disease, specifically:

               -  New York Heart Association > Class II congestive heart failure that is not
                  controlled on standard therapy within 6 months prior to initiation of treatment
                  with Toca 511.

               -  Uncontrolled or significant cardiovascular disease, clinically significant
                  ventricular arrhythmia (such as ventricular tachycardia, ventricular
                  fibrillation, or Torsades de pointes), clinically significant pulmonary disease
                  (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03).

               -  Any other disease, either metabolic or psychological, that as per Investigator
                  assessment may affect the patient's compliance or place the patient at an
                  increased risk of potential treatment complications.

          8. Patient has a history of allergy or intolerance to flucytosine.

          9. Patient has a condition that would prevent him or her from being able to swallow Toca
             FC tablets or absorb flucytosine.

         10. Patient is human immunodeficiency virus seropositive.

         11. Patient is breast feeding.

         12. Patient has previously participated in the Toca 5 trial (Tg 511-15-01).
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Changes from baseline in immune activity in tumor and peripheral blood
Time Frame:Baseline to Weeks 9-10
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tocagen Inc.

Trial Keywords

  • Anaplastic Astrocytoma, Glioblastoma

Last Updated

September 5, 2017