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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
100 Years
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
22/05/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/02/2025
Actual
Sample size
Target
Accrual to date
Final
167
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
Bruxelles
Country [5] 0 0
Belgium
State/province [5] 0 0
Edegem
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.


Results not provided in https://clinicaltrials.gov/study/NCT03798626