Clinical Trials /

CBP501, Cisplatin and Nivolumab in Advanced Refractory Tumors

NCT03113188

Description:

This is a multicenter, open-label, phase 1b study of CBP501/cisplatin/nivolumab combination administered once every 21 days to patients with advanced solid tumors.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CBP501, Cisplatin and Nivolumab in Advanced Refractory Tumors
  • Official Title: Phase 1b Clinical Study of CBP501, Cisplatin and Nivolumab Administered Every 3 Weeks in Patients With Advanced Refractory Tumors

Clinical Trial IDs

  • ORG STUDY ID: CBP17-01
  • NCT ID: NCT03113188

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
CBP501CBP501, CDDP, Nivolumab

Purpose

This is a multicenter, open-label, phase 1b study of CBP501/cisplatin/nivolumab combination administered once every 21 days to patients with advanced solid tumors.

Detailed Description

      Multicenter, open-label, phase 1b study of CBP501/cisplatin/nivolumab combination
      administered once every 21 days to patients with advanced solid tumors. The study will be
      conducted in two parts.

      The first part of the study involves dose-escalation, in which successive cohorts of three
      patients (expanded up to six patients in the event of a dose-limiting toxicity (DLT) or
      safety concerns) will receive escalating doses of CBP501 and/or cisplatin until the maximum
      tolerated dose (MTD) is reached or RP2D defined, based on tolerability observed during the
      first 21 days of treatment and safety review of all available information by the Safety
      Monitoring Committee.

      The second part of the study involves treatment of expansion cohorts of 10 evaluable patients
      each in pretreated metastatic exocrine pancreatic cancer and in microsatellite stable
      colorectal cancer to confirm the tolerability of treatment at the RP2D and evaluate
      preliminary evidence of anti-tumor activity in these indications.
    

Trial Arms

NameTypeDescriptionInterventions
CBP501, CDDP, NivolumabExperimentalCBP501, Cisplatin and Nivolumab Administered Every 3 Weeks in Patients with Advanced Refractory Tumors
  • CBP501

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent obtained prior to initiation of any study-specific procedures
             and treatment;

          2. Previously treated, pathologically confirmed, locally advanced or metastatic solid
             tumors with measurable disease for which cisplatin is a reasonable treatment option,
             including, but not limited to, non-small cell lung, mesothelioma, head & neck,
             ovarian, endometrial, breast, bladder, kidney, esophageal, gastric, colon, liver,
             gallbladder, cholangiocarcinoma, pancreas, soft tissue sarcoma, and osteosarcoma (for
             the expansion cohorts, only metastatic exocrine pancreatic cancer and microsatellite
             stable colorectal cancer are allowed). There is no limit on the number of prior lines
             of chemotherapy (including prior cisplatin), chemoradiotherapy, radiotherapy or
             investigational agents the patient can have received in order to be eligible, as long
             as cisplatin is a reasonable treatment option and all eligibility criteria are met,
             with the exception that a patient must not have received more than two prior lines
             incorporating anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade.

             Patients who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune
             checkpoint blockade therapy must have tolerated therapy with no evidence of grade 4
             toxicity or an immune-related event (any grade) that required treatment
             discontinuation. Patients who experienced an endocrine related dysfunction are
             eligible, provided they are on stable hormone replacement therapy;

          3. Male or female patients aged ≥ 18 years at time of informed consent;

          4. ECOG Performance Status (PS) 0-1;

          5. Life expectancy > 3 months;

          6. Previous anticancer treatment must be discontinued at least 3 weeks prior to the
             initiation of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen
             therapy if discontinued prior to treatment initiation, except 8 weeks for
             bicalutamide);

          7. Adequate bone marrow reserve, cardiac, liver, renal and metabolic function:

               -  absolute neutrophil count (ANC) ≥ 1.5 x 109/L;

               -  platelet count ≥ 100 x 109/L;

               -  hemoglobin ≥ 9 g/dL;

               -  white blood cell count (WBC) ≤ upper limit of normal (ULN);

               -  creatinine phosphokinase isozymes CPK-MB and CPK-MM

                  ≤ ULN;

               -  serum troponin T levels within normal limits;

               -  bilirubin ≤ 1.5 x ULN;

               -  alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) ≤
                  2.5 x ULN (≤ 5 x ULN if liver metastases are present);

               -  INR ≤ 1.5 x ULN;

               -  serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min (by Cockroft & Gault
                  formula or alternate calculation by 24hr urine collection);

               -  serum potassium NCI-CTCAE version 4.03 Grade <2;

               -  serum calcium NCI-CTCAE version 4.03 Grade <2;

               -  serum magnesium NCI-CTCAE version 4.03 Grade <2;

          8. Female patients of child-bearing potential must have a negative serum pregnancy test
             and use at least one form of contraception as approved by the investigator for 4 weeks
             prior to initiating study treatment and 4 months after the last dose of study drug.
             For the purposes of this study, child-bearing potential is defined as "all female
             patients unless they are post-menopausal for at least 3 years or surgically sterile";

          9. Male patients must use a form of barrier contraception approved by the investigator
             during the study and for 4 months after the last dose of study drug;

         10. Ability to cooperate with study treatment and follow-up.

        Exclusion Criteria

          1. Radiation therapy to >30% of bone marrow prior to study entry;

          2. Prior chemotherapy with nitrosoureas, prior mitomycin C cumulative dose ≥ 25 mg/m2,
             prior bone marrow transplant, or prior intensive chemotherapy with stem cell support;

          3. Presence of any serious concomitant systemic disorders incompatible with the study in
             the opinion of the investigator (e.g., uncontrolled congestive heart failure, active
             infection, etc.);

          4. Any previous history of another malignancy (other than cured basal cell or squamous
             cell carcinoma of the skin or cured in-situ carcinoma) within 5 years of study entry;

          5. Presence of any significant central nervous system (CNS) or psychiatric disorder(s)
             that would hamper the patient's compliance;

          6. Evidence of peripheral neuropathy > grade 1 by NCI-CTCAE version 4.03;

          7. Treatment with any other investigational agent or participation in another clinical
             trial within 28 days prior to study entry;

          8. Pregnant or breast-feeding patients or any patient with child-bearing potential not
             using adequate contraception;

          9. Known HIV, HBV, or HCV infection (excluding cured HCV infection);

         10. Active CNS metastases; however, patients with CNS metastases will be eligible if they
             have been treated and are stable without symptoms for 4 weeks after completion of
             treatment, with image documentation required, and must be off steroids;

         11. Who require chronic systemic steroid therapy or on any other form of immunosuppressive
             medication;

         12. Has received a live-virus vaccination within 30 days of planned treatment start;

         13. With known risk factors for bowel perforation, i.e., history of diverticulitis,
             intra-abdominal abscess, intestinal obstruction, or abdominal carcinomatosis;

         14. Has an active autoimmune disease or a documented history of autoimmune disease;

         15. Has a history pneumonitis or interstitial lung disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended dose
Time Frame:21 days
Safety Issue:
Description:Define the recommended doses (RD) of CBP501, cisplatin and nivolumab when administered in combination once every 21 days in patients with previously treated advanced solid tumors

Secondary Outcome Measures

Measure:Hint of efficacy in pretreated pancreatic and micro-satellite stable colorectal cancer patients
Time Frame:through study completion, an average of 6 month
Safety Issue:
Description:Overall response rate will be analyzed according to Simon optimal stage 1 design

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:CanBas Co. Ltd.

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