Clinical trial NCT03798626: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Gastroesophageal Cancer
Renal Cell Carcinoma
Keywords: colorectal cancer
gastroesophageal cancer
renal cell carcinoma
gevokizumab
bevacizumab
modified FOLFOX6
FOLFIRI
ramucirumab
paclitaxel
cabozantinib
CRC
GEC
RCC
VPM087
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-01-10
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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

Primary outcomes:
measure: Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy
timeFrame: Baseline, Day 15
measure: Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]
timeFrame: First 4 weeks of combination treatment
measure: Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]
timeFrame: First 6 weeks of combination treatment
measure: Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]
timeFrame: At 15 months
measure: Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]
timeFrame: At 9 months
measure: Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]
timeFrame: At 6 months
Secondary outcomes:
measure: Overall response rate (ORR) per investigator assessment using RECIST v1.1
timeFrame: Up to 5 years
measure: Duration of response (DOR) per investigator assessment using RECIST v1.1
timeFrame: Up to 5 years
measure: Disease Control Rate (DCR) per investigator assessment using RECIST v1.1
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]
timeFrame: Up to 5 years
measure: PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)
timeFrame: Up to 5 years
measure: Serum concentration of gevokizumab, as monotherapy and in the combination regimens
timeFrame: Up to 5 years
measure: Serum concentration of bevacizumab
timeFrame: Up to 5 years
measure: Serum concentration of ramucirumab
timeFrame: Up to 5 years
measure: Serum concentration of irinotecan
timeFrame: Up to 3 months
measure: Serum concentration of paclitaxel
timeFrame: Up to 3 months
measure: Serum concentration of cabozantinib
timeFrame: Up to 3 months
measure: Number of patients with anti-drug antibodies for gevokizumab in the combination regimens
timeFrame: Up to 5 years
measure: Number of patients with anti-drug antibodies for bevacizumab in the combination regimens
timeFrame: Up to 5 years
measure: Number of patients with anti-drug antibodies for ramucirumab in the combination regimens
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California LA
state: California
city: Saint Louis
country: United States
facility: WA Uni School Of Med
state: Missouri
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Sunto Gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: