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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 )

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Gastroesophageal Cancer Renal Cell Carcinoma Drug: Gevokizumab Drug: Bevacizumab Drug: Modified FOLFOX6 Drug: FOLFIRI Drug: Ramucirumab Drug: Paclitaxel Drug: Cabozantinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 22, 2019
Estimated Primary Completion Date : May 17, 2022
Estimated Study Completion Date : December 18, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1st line colorectal cancer
Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
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

Experimental: 2nd line colorectal cancer
Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
Drug: Gevokizumab
60 mg/mL concentration; administered intravenously (IV)
Other Name: VPM087

Drug: Bevacizumab
25 mg/mL concentration; administered IV

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

Experimental: 2nd line gastroesophageal cancer
Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
Drug: Gevokizumab
60 mg/mL concentration; administered intravenously (IV)
Other Name: VPM087

Drug: Ramucirumab
10 mg/mL concentration; administered IV

Drug: Paclitaxel
6 mg/mL concentration; administered IV

Experimental: 2nd or 3rd line renal cell carcinoma
Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
Drug: Gevokizumab
60 mg/mL concentration; administered intravenously (IV)
Other Name: VPM087

Drug: Cabozantinib
60 mg tablet; administered orally




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Serum concentration of gevokizumab, as monotherapy and in the combination regimens [ Time Frame: Up to 5 years ]
    To characterize the pharmacokinetics of gevokizumab therapy

  6. Serum concentration of bevacizumab [ Time Frame: Up to 5 years ]
    To characterize the pharmacokinetics of bevacizumab therapy

  7. Serum concentration of ramucirumab [ Time Frame: Up to 5 years ]
    To characterize the pharmacokinetics of ramucirumab therapy

  8. Serum concentration of irinotecan [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of irinotecan therapy

  9. Serum concentration of paclitaxel [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of paclitaxel therapy

  10. Serum concentration of cabozantinib [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of cabozantinib therapy

  11. Number of patients with anti-drug antibodies for gevokizumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for gevokizumab

  12. Number of patients with anti-drug antibodies for bevacizumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for bevacizumab

  13. Number of patients with anti-drug antibodies for ramucirumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for ramucirumab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03798626


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

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Locations
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United States, Arizona
Mayo Clinic Arizona Reg-2 Recruiting
Phoenix, Arizona, United States, 85054
Principal Investigator: Tanios Bekaii Saab         
United States, Tennessee
Sarah Cannon Research Institute Drug Ship - 4 Recruiting
Nashville, Tennessee, United States, 37203
Contact: Caleb Cleveland    +1 615 329 7274    Caleb.Cleveland@sarahcannon.com   
Principal Investigator: Johanna Chock Bendell         
Australia, South Austrailia
Novartis Investigative Site Recruiting
Woodville, South Austrailia, Australia, 5011
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Austria
Novartis Investigative Site Recruiting
Salzburg, Austria, 5020
Novartis Investigative Site Recruiting
Wien, Austria, A-1090
Belgium
Novartis Investigative Site Recruiting
Edegem, Belgium, 2650
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1Z6
Czechia
Novartis Investigative Site Recruiting
Brno, Czech Republic, Czechia, 656 53
Germany
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Ulm, Germany, 89081
Hong Kong
Novartis Investigative Site Recruiting
Pokfulam, Hong Kong
Israel
Novartis Investigative Site Recruiting
Ramat Gan, Israel, 5265601
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20162
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 464 8681
Novartis Investigative Site Recruiting
Kashiwa, Chiba, Japan, 277 8577
Novartis Investigative Site Recruiting
Sunto Gun, Shizuoka, Japan, 411 8777
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 05505
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119074
Spain
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46010
Novartis Investigative Site Recruiting
Barcelona, Spain, 08907
Novartis Investigative Site Recruiting
Madrid, Spain, 28009
Novartis Investigative Site Recruiting
Madrid, Spain, 28034
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Taiwan
Novartis Investigative Site Recruiting
Tainan, Taiwan, 70403
United Kingdom
Novartis Investigative Site Recruiting
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03798626     History of Changes
Other Study ID Numbers: CVPM087A2101
2018-003952-19 ( EudraCT Number )
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
colorectal cancer
gastroesophageal cancer
gevokizumab
renal cell carcinoma
bevacizumab
modified FOLFOX6
FOLFIRI
ramucirumab
paclitaxel
cabozantinib
CRC
GEC
RCC
VPM087
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Carcinoma
Carcinoma, Renal Cell
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Adenocarcinoma
Kidney Diseases
Urologic Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Oxaliplatin
Irinotecan
Fluorouracil
Ramucirumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents