Clinical Trials /

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers

NCT03798626

Description:

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose and preliminary efficacy of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Colorectal Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers
  • Official Title: Phase Ib Study of Gevokizumab in Combination With Standard of Care Anti-cancer Therapies in Patients With Metastatic Colorectal Cancer, Gastroesophageal Cancer and Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: CVPM087A2101
  • SECONDARY ID: 2018-003952-19
  • NCT ID: NCT03798626

Conditions

  • Colorectal Cancer
  • Gastroesophageal Cancer
  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
GevokizumabVPM0871st line colorectal cancer
Bevacizumab1st line colorectal cancer
Modified FOLFOX6oxaliplatin, leucovorin, 5-fluorouracil1st line colorectal cancer
FOLFIRIirinotecan, leucovorin, 5-fluorouracil2nd line colorectal cancer
Ramucirumab2nd line gastroesophageal cancer
Paclitaxel2nd line gastroesophageal cancer
Cabozantinib2nd or 3rd line renal cell carcinoma

Purpose

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose and preliminary efficacy of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma.

Trial Arms

NameTypeDescriptionInterventions
1st line colorectal cancerExperimentalTreatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
  • Gevokizumab
  • Bevacizumab
  • Modified FOLFOX6
2nd line colorectal cancerExperimentalTreatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
  • Gevokizumab
  • Bevacizumab
  • FOLFIRI
2nd line gastroesophageal cancerExperimentalTreatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
  • Gevokizumab
  • Ramucirumab
  • Paclitaxel
2nd or 3rd line renal cell carcinomaExperimentalTreatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
  • Gevokizumab
  • Cabozantinib

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic disease not amenable to potentially curative surgery and with available
             archival tumor tissue or fresh tumor tissue biopsy.

          -  Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST
             1.1.

        For Cohort A:

        - First line metastatic colorectal cancer.

        For Cohort B:

        - Second line metastatic colorectal cancer that has progressed on prior chemotherapy
        administered for metastatic disease and which must include a fluoropyrimidine and
        oxaliplatin.

        For Cohort C:

        - Second line metastatic gastroesophageal cancer that has progressed on prior line of
        chemotherapy administered for metastatic disease, and which must include a platinum agent
        and fluoropyrimidine doublet.

        For Cohort D:

        - Second or third line metastatic renal cell carcinoma with a clear-cell component and has
        received one or two lines of treatment for metastatic disease that included an
        anti-angiogenic agent for at least 4 weeks with radiologic progression on that treatment.

        For subjects starting from Part 1a in Cohorts A and B:

          -  Serum hs-CRP at screening ≥ 10 mg/L.

          -  Not requiring immediate initiation of anti-cancer therapy per investigator's best
             judgement.

        For subjects starting from Part 2 in Cohorts C and D:

        - Serum hs-CRP at screening ≥ 10 mg/L.

        Exclusion Criteria:

        For All Cohorts:

          -  Currently receiving any of the prohibited medications or has contraindications as
             outlined in the protocol.

          -  Symptomatic brain metastases or brain metastases that require directed therapy (such
             as focal radiotherapy or surgery).

          -  Suspected or proven immunocompromised state, or infections (as defined in the
             protocol).

          -  Conditions that have a high risk of clinically significant bleeding after
             administration of anti-VEGF agents.

          -  Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular
             disease.

        For Cohort D:

          -  Concomitant medications, herbal supplements, and/or fruits and their juices that are
             known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow
             therapeutic window and are predominantly metabolized through CYP3A4/5.

          -  Impairment of GI function or GI disease that may significantly alter the absorption of
             cabozantinib.

        Other protocol-defined inclusion/exclusion criteria may apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hsCRP) after first dose of gevokizumab monotherapy
Time Frame:Baseline, Day 15
Safety Issue:
Description:Log scale change of hsCRP at Day 15 from baseline

Secondary Outcome Measures

Measure:Part 2 (Expansion): Overall response rate (ORR) per investigator assessment using RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:ORR is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), according to RECIST 1.1
Measure:Part 2 (Expansion): Duration of response (DOR) per investigator assessment using RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria
Measure:Part 2 (Expansion): Disease Control Rate (DCR) per investigator assessment using RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.
Measure:Part 2 (Expansion): Overall survival (OS)
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time from date of first dose of study treatment to date of death due to any cause.
Measure:Serum concentration of gevokizumab, as monotherapy and in the combination regimens
Time Frame:Up to 5 years
Safety Issue:
Description:To characterize the pharmacokinetics of gevokizumab therapy
Measure:Serum concentration of bevacizumab
Time Frame:Up to 5 years
Safety Issue:
Description:To characterize the pharmacokinetics of bevacizumab therapy
Measure:Serum concentration of ramucirumab
Time Frame:Up to 5 years
Safety Issue:
Description:To characterize the pharmacokinetics of ramucirumab therapy
Measure:Serum concentration of irinotecan
Time Frame:Up to 3 months
Safety Issue:
Description:To characterize the pharmacokinetics of irinotecan therapy
Measure:Serum concentration of paclitaxel
Time Frame:Up to 3 months
Safety Issue:
Description:To characterize the pharmacokinetics of paclitaxel therapy
Measure:Serum concentration of cabozantinib
Time Frame:Up to 3 months
Safety Issue:
Description:To characterize the pharmacokinetics of cabozantinib therapy
Measure:Number of patients with anti-drug antibodies for gevokizumab in the combination regimens
Time Frame:Up to 5 years
Safety Issue:
Description:Incidence of immunogenicity for gevokizumab
Measure:Number of patients with anti-drug antibodies for bevacizumab in the combination regimens
Time Frame:Up to 5 years
Safety Issue:
Description:Incidence of immunogenicity for bevacizumab
Measure:Number of patients with anti-drug antibodies for ramucirumab in the combination regimens
Time Frame:Up to 5 years
Safety Issue:
Description:Incidence of immunogenicity for ramucirumab

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • colorectal cancer
  • gastroesophageal cancer
  • renal cell carcinoma
  • gevokizumab
  • bevacizumab
  • modified FOLFOX6
  • FOLFIRI
  • ramucirumab
  • paclitaxel
  • cabozantinib
  • CRC
  • GEC
  • RCC
  • VPM087

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