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

NCT ID: NCT03798626

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-22
• Study Completion Date: 2025-02-05

Brief Summary

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose 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, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.

Conditions

Colorectal Cancer; Gastroesophageal Cancer; Renal Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: 1st line colorectal cancer

Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab

Group Type: EXPERIMENTAL

Gevokizumab

Intervention Type: DRUG

60 mg/mL concentration; administered intravenously (IV)

Bevacizumab

Intervention Type: DRUG

25 mg/mL concentration; administered IV

Modified FOLFOX6

Intervention Type: DRUG

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 \[50 mg/mL concentration; administered IV\]

Cohort B: 2nd line colorectal cancer

Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab

Group Type: EXPERIMENTAL

Gevokizumab

Intervention Type: DRUG

60 mg/mL concentration; administered intravenously (IV)

Bevacizumab

Intervention Type: DRUG

25 mg/mL concentration; administered IV

FOLFIRI

Intervention Type: DRUG

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 \[50 mg/mL concentration; administered IV\]

Cohort C: 2nd line gastroesophageal cancer

Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab

Group Type: EXPERIMENTAL

Gevokizumab

Intervention Type: DRUG

60 mg/mL concentration; administered intravenously (IV)

Ramucirumab

Intervention Type: DRUG

10 mg/mL concentration; administered IV

Paclitaxel

Intervention Type: DRUG

6 mg/mL concentration; administered IV

Cohort D: 2nd or 3rd line renal cell carcinoma

Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib

Group Type: EXPERIMENTAL

Gevokizumab

Intervention Type: DRUG

60 mg/mL concentration; administered intravenously (IV)

Cabozantinib

Intervention Type: DRUG

60 mg tablet; administered orally

Interventions

Gevokizumab

60 mg/mL concentration; administered intravenously (IV)

Intervention Type: DRUG

Bevacizumab

25 mg/mL concentration; administered IV

Intervention Type: 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 \[50 mg/mL concentration; administered IV\]

Intervention Type: 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 \[50 mg/mL concentration; administered IV\]

Intervention Type: DRUG

Ramucirumab

10 mg/mL concentration; administered IV

Intervention Type: DRUG

Paclitaxel

6 mg/mL concentration; administered IV

Intervention Type: DRUG

Cabozantinib

60 mg tablet; administered orally

Intervention Type: DRUG

Other Intervention Names

VPM087; oxaliplatin, leucovorin, 5-fluorouracil; irinotecan, leucovorin, 5-fluorouracil

Eligibility Criteria

Inclusion Criteria

For All Cohorts:

• Adult ≥ 18 years old.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Adequate bone marrow and organ function per defined criteria in the protocol.
• Recovered from acute laboratory and clinical toxicities of prior anti cancer treatment to NCI CTCAE v5.0 grade ≤1 at time of screening, except alopecia and amenorrhea.

For Cohort A:

• First line metastatic colorectal adenocarcinoma.

For Cohort B:

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

For Cohort C:

• Second line metastatic gastroesophageal adenocarcinoma 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 (per central laboratory assessment).
• Not requiring immediate initiation of anti cancer therapy per investigator's best judgement.

For subjects starting from Part 2 in Cohort C:

• Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).

Exclusion Criteria

For All Cohorts:

• Currently receiving any of the prohibited medications or has contraindications as outlined in the 'Contraindications' to SOC regimen components.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

University of California LA

Los Angeles, California, United States

WA Uni School Of Med

St Louis, Missouri, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Edegem, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Calgary, Alberta, Canada

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Santiago, , Chile

Novartis Investigative Site

Brno, , Czechia

Novartis Investigative Site

Frankfurt am Main, Hesse, Germany

Novartis Investigative Site

Dresden, Saxony, Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Kashiwa, Chiba, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Sunto Gun, Shizuoka, Japan

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Seville, , Spain

Novartis Investigative Site

Valencia, , Spain

Novartis Investigative Site

Tainan, , Taiwan

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Chile; Czechia; Germany; Israel; Italy; Japan; Singapore; South Korea; Spain; Taiwan; United Kingdom

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18408

Novartis Pharma AG results

Other Identifiers

2018-003952-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVPM087A2101

Identifier Type: -

Identifier Source: org_study_id