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

Colorectal Cancer Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03798626
• Other study ID #: CVPM087A2101
• Secondary ID: 2018-003952-19
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 22, 2019
• Est. completion date: October 28, 2024

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 167
• Est. completion date: October 28, 2024
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Cohort C:

• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Colorectal Cancer
• Colorectal Neoplasms
• Gastroesophageal Cancer
• Renal Cell Carcinoma

Intervention

Drug:
• Gevokizumab
60 mg/mL concentration; administered intravenously (IV)
• Bevacizumab
25 mg/mL concentration; administered IV
• 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]
• 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]
• Ramucirumab
10 mg/mL concentration; administered IV
• Paclitaxel
6 mg/mL concentration; administered IV
• Cabozantinib
60 mg tablet; administered orally

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Toronto	Ontario
Chile	Novartis Investigative Site	Santiago
Czechia	Novartis Investigative Site	Brno	Czech Republic
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Ulm
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Kashiwa	Chiba
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sunto Gun	Shizuoka
Korea, Republic of	Novartis Investigative Site	Seoul
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Taiwan	Novartis Investigative Site	Tainan
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United States	University Of California Los Angeles UCLA Oncology Clinic	Los Angeles	California
United States	Sarah Cannon Research Institute Drug Ship - 4	Nashville	Tennessee
United States	Washington Uni School of Med Siteman Cancer Center	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Chile,  Czechia,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy	Log scale change of hs-CRP at Day 15 from baseline	Baseline, Day 15
Primary	Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]	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.	First 4 weeks of combination treatment
Primary	Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]	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.	First 6 weeks of combination treatment
Primary	Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]	PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.	At 15 months
Primary	Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]	PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.	At 9 months
Primary	Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]	PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.	At 6 months
Secondary	Overall response rate (ORR) per investigator assessment using RECIST v1.1	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	Up to 5 years
Secondary	Duration of response (DOR) per investigator assessment using RECIST v1.1	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	Up to 5 years
Secondary	Disease Control Rate (DCR) per investigator assessment using RECIST v1.1	DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.	Up to 5 years
Secondary	Overall survival (OS)	OS is defined as the time from date of first dose of study treatment to date of death due to any cause.	Up to 5 years
Secondary	PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]	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.	Up to 5 years
Secondary	PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)	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.	Up to 5 years
Secondary	Serum concentration of gevokizumab, as monotherapy and in the combination regimens	To characterize the pharmacokinetics of gevokizumab therapy	Up to 5 years
Secondary	Serum concentration of bevacizumab	To characterize the pharmacokinetics of bevacizumab therapy	Up to 5 years
Secondary	Serum concentration of ramucirumab	To characterize the pharmacokinetics of ramucirumab therapy	Up to 5 years
Secondary	Serum concentration of irinotecan	To characterize the pharmacokinetics of irinotecan therapy	Up to 3 months
Secondary	Serum concentration of paclitaxel	To characterize the pharmacokinetics of paclitaxel therapy	Up to 3 months
Secondary	Serum concentration of cabozantinib	To characterize the pharmacokinetics of cabozantinib therapy	Up to 3 months
Secondary	Number of patients with anti-drug antibodies for gevokizumab in the combination regimens	Incidence of immunogenicity for gevokizumab	Up to 5 years
Secondary	Number of patients with anti-drug antibodies for bevacizumab in the combination regimens	Incidence of immunogenicity for bevacizumab	Up to 5 years
Secondary	Number of patients with anti-drug antibodies for ramucirumab in the combination regimens	Incidence of immunogenicity for ramucirumab	Up to 5 years