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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03798626

Studienbeginn:
Mai 2019

Letztes Update:
19.10.2020

Wirkstoff:
Gevokizumab, Bevacizumab, Modified FOLFOX6, FOLFIRI, Ramucirumab, Paclitaxel, Cabozantinib

Indikation (Clinical Trials):
Carcinoma, Colorectal Neoplasms, Carcinoma, Renal Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Studienlocations (3 von 38)

Novartis Investigative Site
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
89081 Ulm
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
University of California at Los Angeles UCLA Oncology Clinic
90095 Los Angeles
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Dana Taylor-Williams
Phone: 310-825-4493
E-Mail: dtaylor@mednet.ucla.edu
» Ansprechpartner anzeigen
Sarah Cannon Research Institute Drug Ship - 4
37203 Nashville
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Andrew Nichols
Phone: +1 615 329 7274
E-Mail: Andrew.Nichols@sarahcannon.com
» Ansprechpartner anzeigen
Novartis Investigative Site
5011 Woodville
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
1000 Bruxelles
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
M5G 1Z6 Toronto
CanadaRekrutierend» Google-Maps
Novartis Investigative Site
8330074 Santiago
ChileAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
52621 Ramat Gan
IsraelRekrutierend» Google-Maps
Novartis Investigative Site
6423906 Tel Aviv
IsraelRekrutierend» Google-Maps
Novartis Investigative Site
277 8577 Kashiwa
JapanRekrutierend» Google-Maps
Novartis Investigative Site
541-8567 Osaka-city
JapanRekrutierend» Google-Maps
Novartis Investigative Site
411 8777 Sunto Gun
JapanRekrutierend» Google-Maps
Novartis Investigative Site
05505 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Novartis Investigative Site
119074 Singapore
SingaporeRekrutierend» Google-Maps
Novartis Investigative Site
SW3 6JJ London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose and preliminary efficacy 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.

Ein-/Ausschlusskriterien

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 Cohorts C and D:

- 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

Studien-Rationale

Primary outcome:

1. Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hsCRP) after first dose of gevokizumab monotherapy (Time Frame - Baseline, Day 15):
Log scale change of hsCRP at Day 15 from baseline

2. Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [mGEC & mRCC] (Time Frame - First 4 weeks of combination treatment):
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.

3. Part 1b (Safety run-in): Number of DLTs [1st line mCRC and 2nd line mCRC] (Time Frame - First 6 weeks of combination treatment):
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.

4. Part 2 (Expansion): Progression free survival (PFS) rate per investigator assessment using RECIST v1.1 [mGEC] (Time Frame - 24 weeks):
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.

5. Part 2 (Expansion): Progression free survival (PFS) rate per investigator assessment using RECIST v1.1 [2nd line mCRC & mRCC] (Time Frame - 40 weeks):
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.

6. Part 2 (Expansion): Progression free survival (PFS) rate per investigator assessment using RECIST v1.1 [1st line mCRC] (Time Frame - 64 weeks):
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.

Secondary outcome:

1. Part 2 (Expansion): Overall response rate (ORR) per investigator assessment using RECIST v1.1 (Time Frame - Up to 5 years):
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

2. Part 2 (Expansion): Duration of response (DOR) per investigator assessment using RECIST v1.1 (Time Frame - Up to 5 years):
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

3. Part 2 (Expansion): Disease Control Rate (DCR) per investigator assessment using RECIST v1.1 (Time Frame - Up to 5 years):
DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.

4. Part 2 (Expansion): Overall survival (OS) (Time Frame - Up to 5 years):
OS is defined as the time from date of first dose of study treatment to date of death due to any cause.

5. Serum concentration of gevokizumab, as monotherapy and in the combination regimens (Time Frame - Up to 5 years):
To characterize the pharmacokinetics of gevokizumab therapy

6. Serum concentration of bevacizumab (Time Frame - Up to 5 years):
To characterize the pharmacokinetics of bevacizumab therapy

7. Serum concentration of ramucirumab (Time Frame - Up to 5 years):
To characterize the pharmacokinetics of ramucirumab therapy

8. Serum concentration of irinotecan (Time Frame - Up to 3 months):
To characterize the pharmacokinetics of irinotecan therapy

9. Serum concentration of paclitaxel (Time Frame - Up to 3 months):
To characterize the pharmacokinetics of paclitaxel therapy

10. Serum concentration of cabozantinib (Time Frame - Up to 3 months):
To characterize the pharmacokinetics of cabozantinib therapy

11. Number of patients with anti-drug antibodies for gevokizumab in the combination regimens (Time Frame - Up to 5 years):
Incidence of immunogenicity for gevokizumab

12. Number of patients with anti-drug antibodies for bevacizumab in the combination regimens (Time Frame - Up to 5 years):
Incidence of immunogenicity for bevacizumab

13. Number of patients with anti-drug antibodies for ramucirumab in the combination regimens (Time Frame - Up to 5 years):
Incidence of immunogenicity for ramucirumab

Studien-Arme

  • Experimental: 1st line colorectal cancer
    Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
  • Experimental: 2nd line colorectal cancer
    Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
  • Experimental: 2nd line gastroesophageal cancer
    Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
  • Experimental: 2nd or 3rd line renal cell carcinoma
    Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib

Geprüfte Regime

  • Gevokizumab (VPM087):
    60 mg/mL concentration; administered intravenously (IV)
  • Bevacizumab:
    25 mg/mL concentration; administered IV
  • Modified FOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil):
    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, leucovorin, 5-fluorouracil):
    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

Quelle: ClinicalTrials.gov


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