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

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ClinicalTrials.gov Identifier: NCT03798626
Recruitment Status : Recruiting
First Posted : January 10, 2019
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 7, 2019
First Posted Date  ICMJE January 10, 2019
Last Update Posted Date December 3, 2019
Actual Study Start Date  ICMJE May 22, 2019
Estimated Primary Completion Date May 17, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2019)
  • Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hsCRP) after first dose of gevokizumab monotherapy [ Time Frame: Baseline, Day 15 ]
    Log scale change of hsCRP at Day 15 from baseline
  • Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [mGEC & mRCC] [ Time Frame: First 4 weeks of combination treatment ]
    DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
  • Part 1b (Safety run-in): Number of DLTs [1st line mCRC and 2nd line mCRC] [ Time Frame: First 6 weeks of combination treatment ]
    DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
  • Part 2 (Expansion): Progression free survival (PFS) per investigator assessment using RECIST v1.1 [mGEC] [ Time Frame: 24 weeks ]
    PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
  • Part 2 (Expansion): Progression free survival (PFS) per investigator assessment using RECIST v1.1 [2nd line mCRC & mRCC] [ Time Frame: 40 weeks ]
    PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
  • Part 2 (Expansion): Progression free survival (PFS) per investigator assessment using RECIST v1.1 [1st line mCRC] [ Time Frame: 64 weeks ]
    PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03798626 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2019)
  • Part 2 (Expansion): Overall response rate (ORR) per investigator assessment using RECIST v1.1 [ Time Frame: Up to 5 years ]
    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
  • Part 2 (Expansion): Duration of response (DOR) per investigator assessment using RECIST v1.1 [ Time Frame: Up to 5 years ]
    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
  • Part 2 (Expansion): Disease Control Rate (DCR) per investigator assessment using RECIST v1.1 [ Time Frame: Up to 5 years ]
    DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.
  • Part 2 (Expansion): Overall survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time from date of first dose of study treatment to date of death due to any cause.
  • Serum concentration of gevokizumab, as monotherapy and in the combination regimens [ Time Frame: Up to 5 years ]
    To characterize the pharmacokinetics of gevokizumab therapy
  • Serum concentration of bevacizumab [ Time Frame: Up to 5 years ]
    To characterize the pharmacokinetics of bevacizumab therapy
  • Serum concentration of ramucirumab [ Time Frame: Up to 5 years ]
    To characterize the pharmacokinetics of ramucirumab therapy
  • Serum concentration of irinotecan [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of irinotecan therapy
  • Serum concentration of paclitaxel [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of paclitaxel therapy
  • Serum concentration of cabozantinib [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of cabozantinib therapy
  • Number of patients with anti-drug antibodies for gevokizumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for gevokizumab
  • Number of patients with anti-drug antibodies for bevacizumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for bevacizumab
  • Number of patients with anti-drug antibodies for ramucirumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for ramucirumab
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Gastroesophageal Cancer
  • Renal Cell Carcinoma
Intervention  ICMJE
  • Drug: Gevokizumab
    60 mg/mL concentration; administered intravenously (IV)
    Other Name: VPM087
  • Drug: Bevacizumab
    25 mg/mL concentration; administered IV
  • Drug: Modified FOLFOX6
    Oxaliplatin [5 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]
    Other Name: oxaliplatin, leucovorin, 5-fluorouracil
  • Drug: FOLFIRI
    Irinotecan [20 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]
    Other Name: irinotecan, leucovorin, 5-fluorouracil
  • Drug: Ramucirumab
    10 mg/mL concentration; administered IV
  • Drug: Paclitaxel
    6 mg/mL concentration; administered IV
  • Drug: Cabozantinib
    60 mg tablet; administered orally
Study Arms  ICMJE
  • Experimental: 1st line colorectal cancer
    Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
    Interventions:
    • Drug: Gevokizumab
    • Drug: Bevacizumab
    • Drug: Modified FOLFOX6
  • Experimental: 2nd line colorectal cancer
    Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
    Interventions:
    • Drug: Gevokizumab
    • Drug: Bevacizumab
    • Drug: FOLFIRI
  • Experimental: 2nd line gastroesophageal cancer
    Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
    Interventions:
    • Drug: Gevokizumab
    • Drug: Ramucirumab
    • Drug: Paclitaxel
  • Experimental: 2nd or 3rd line renal cell carcinoma
    Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
    Interventions:
    • Drug: Gevokizumab
    • Drug: Cabozantinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 7, 2019)
172
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 18, 2023
Estimated Primary Completion Date May 17, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   Germany,   Hong Kong,   Israel,   Italy,   Japan,   Korea, Republic of,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03798626
Other Study ID Numbers  ICMJE CVPM087A2101
2018-003952-19 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP