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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03798626




Registration number
NCT03798626
Ethics application status
Date submitted
7/01/2019
Date registered
10/01/2019

Titles & IDs
Public title
Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers
Scientific 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
Secondary ID [1] 0 0
2018-003952-19
Secondary ID [2] 0 0
CVPM087A2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Gastroesophageal Cancer 0 0
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gevokizumab
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Modified FOLFOX6
Treatment: Drugs - FOLFIRI
Treatment: Drugs - Ramucirumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cabozantinib

Experimental: Cohort A: 1st line colorectal cancer - Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab

Experimental: Cohort B: 2nd line colorectal cancer - Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab

Experimental: Cohort C: 2nd line gastroesophageal cancer - Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab

Experimental: Cohort D: 2nd or 3rd line renal cell carcinoma - Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib


Treatment: Drugs: Gevokizumab
60 mg/mL concentration; administered intravenously (IV)

Treatment: Drugs: Bevacizumab
25 mg/mL concentration; administered IV

Treatment: Drugs: 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 \[50 mg/mL concentration; administered IV\]

Treatment: Drugs: 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 \[50 mg/mL concentration; administered IV\]

Treatment: Drugs: Ramucirumab
10 mg/mL concentration; administered IV

Treatment: Drugs: Paclitaxel
6 mg/mL concentration; administered IV

Treatment: Drugs: Cabozantinib
60 mg tablet; administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy
Timepoint [1] 0 0
Baseline, Day 15
Primary outcome [2] 0 0
Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]
Timepoint [2] 0 0
First 4 weeks of combination treatment
Primary outcome [3] 0 0
Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]
Timepoint [3] 0 0
First 6 weeks of combination treatment
Primary outcome [4] 0 0
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]
Timepoint [4] 0 0
At 15 months
Primary outcome [5] 0 0
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]
Timepoint [5] 0 0
At 9 months
Primary outcome [6] 0 0
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]
Timepoint [6] 0 0
At 6 months
Secondary outcome [1] 0 0
Overall response rate (ORR) per investigator assessment using RECIST v1.1
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Duration of response (DOR) per investigator assessment using RECIST v1.1
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Disease Control Rate (DCR) per investigator assessment using RECIST v1.1
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Serum concentration of gevokizumab, as monotherapy and in the combination regimens
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Serum concentration of bevacizumab
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
Serum concentration of ramucirumab
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
Serum concentration of irinotecan
Timepoint [10] 0 0
Up to 3 months
Secondary outcome [11] 0 0
Serum concentration of paclitaxel
Timepoint [11] 0 0
Up to 3 months
Secondary outcome [12] 0 0
Serum concentration of cabozantinib
Timepoint [12] 0 0
Up to 3 months
Secondary outcome [13] 0 0
Number of patients with anti-drug antibodies for gevokizumab in the combination regimens
Timepoint [13] 0 0
Up to 5 years
Secondary outcome [14] 0 0
Number of patients with anti-drug antibodies for bevacizumab in the combination regimens
Timepoint [14] 0 0
Up to 5 years
Secondary outcome [15] 0 0
Number of patients with anti-drug antibodies for ramucirumab in the combination regimens
Timepoint [15] 0 0
Up to 5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
Belgium
State/province [4] 0 0
Antwerpen
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Chile
State/province [9] 0 0
Santiago
Country [10] 0 0
Czechia
State/province [10] 0 0
Czech Republic
Country [11] 0 0
Germany
State/province [11] 0 0
Dresden
Country [12] 0 0
Germany
State/province [12] 0 0
Frankfurt
Country [13] 0 0
Germany
State/province [13] 0 0
Ulm
Country [14] 0 0
Israel
State/province [14] 0 0
Ramat Gan
Country [15] 0 0
Israel
State/province [15] 0 0
Tel Aviv
Country [16] 0 0
Italy
State/province [16] 0 0
MI
Country [17] 0 0
Japan
State/province [17] 0 0
Aichi
Country [18] 0 0
Japan
State/province [18] 0 0
Chiba
Country [19] 0 0
Japan
State/province [19] 0 0
Osaka
Country [20] 0 0
Japan
State/province [20] 0 0
Shizuoka
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Singapore
State/province [23] 0 0
Singapore
Country [24] 0 0
Spain
State/province [24] 0 0
Andalucia
Country [25] 0 0
Spain
State/province [25] 0 0
Catalunya
Country [26] 0 0
Spain
State/province [26] 0 0
Comunidad Valenciana
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Taiwan
State/province [28] 0 0
Tainan
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.