Advanced Gastric CancerPhase 2PaFLONCT01503372
FLO +/- Pazopanib as First-line Treatment in Advanced Gastric Cancer
A Phase 2 study testing Pazopanib and 5-FU, Oxaliplatin, Leukovorin (FLO) in people with Advanced Gastric Cancer, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
The prognosis of advanced gastric cancer and adenocarcinoma of the gastro-esophageal (GE) junction is poor. Even with modern chemotherapy the median survival ranges around 8-10 months. Inhibition of neoangiogenesis seems to be a very promising approach in gastric cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Gastric Cancer
- What is being tested?
- Pazopanib and 5-FU, Oxaliplatin, Leukovorin (FLO)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2011to 14 Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.
- Age ≥ 18 years.
- Histologically confirmed adenocarcinoma of the stomach or the gastroesophageal junction with either metastatic or locally advanced disease, incurable by operation.
- Eastern Cooperative Oncology Group (ECOG) performance status of < or = 2
- At least one unidimensional, measurable tumor parameter (according to RECIST 1.1)
- No preceding cytotoxic therapy (neoadjuvant or adjuvant treatment allowed if finished > 6 months before inclusion)
Show all 9Show fewer
- Adequate organ system function.
- Men and women must perform an adequate contraception.
- Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
Who cannot join
- Prior malignancy, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix.
- Overexpression of HER-2, defined as IHC 3+ or IHC 2+ and FISH positive.
- Known hypersensitivity against 5-FU, leukovorin, oxaliplatin or other platinum compounds or pazopanib.
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or the absorption of investigational product
- Presence of uncontrolled infection.
Show all 25Show fewer
- Corrected QT interval (QTc) > 480 ms using Bazett's formula.
- History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, NYHA III or IV congestive heart failure.
- Poorly controlled hypertension.
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- Hemoptysis in excess of 2.5 ml within 8 weeks of first dose of study drug.
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
- Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib. A neoadjuvant or adjuvant chemotherapy must be finished at least 6 month before study entry.
- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
- Grade 3 or 4 diarrhea.
- Peripheral polyneuropathy > NCI Grade.
- Pregnant or lactating women.
- Men or women who are planning a pregnancy within the next six months.
- Participation in another clinical trial with investigational agents within the last 30 days prior to study start.
- The patient is a colleague or employed by the study investigator or by an involved institution including the sponsor of the study.
- Patient is detained in a psychiatric unit or imprisoned.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pazopanib With 5-Fluorouracil, Leucovorin and Oxaliplatin (FLO) as 1st-line Treatment in Advanced Gastric Cancer; a Randomized Phase-II-study of the Arbeitsgemeinschaft Internistische Onkologie
The prognosis of advanced gastric cancer and adenocarcinoma of the gastro-esophageal (GE) junction is poor. Even with modern chemotherapy the median survival ranges around 8-10 months.
Inhibition of neoangiogenesis seems to be a very promising approach in gastric cancer.
Read more
Vascular endothelial growth factor (VEGF) acts as one of the most potent stimulating agents of angiogenesis, and several strategies targeting the VEGF signaling pathway have been developed, including anti-VEGF antibodies, soluble receptors binding directly to VEGF ligand, anti-VEGF receptor (VEGFR) antibodies and VEGFR tyrosine kinase inhibitors. The breakthrough in the clinical development of anti-angiogenic therapy against colorectal cancer came in 2003 with a large prospective, randomized clinical trial of bevacizumab, a monoclonal antibody directed against VEGF. Anti-angiogenic therapy has introduced a highly effective, completely new mode of action in this area and is the new standard of care in advanced colorectal cancer.
The concept of VEGF inhibition is also very promising in gastric cancer. Bevacizumab was investigated in combination with irinotecan and cisplatin in a phase-II trial, including 47 patients with gastric and GE-junction carcinoma. Bevacizumab could safely be given and could improve time to tumor progression by 75% compared to historical controls. Several phase-II trials confirm the tolerability and promising efficacy of bevacizumab in gastric cancer (Bevacizumab + Docetaxel/Oxaliplatin; FOLFOX + Bevacizumab; Docetaxel/Cisplatin/Irinotecan + Bevacizumab). These results were so promising that randomized phase-III trials in the 1st-line and perioperative setting are under way (AVAGAST-trial: Cisplatin /Capecitabine +/- bevacizumab 1st line ; MAGIC-B-trial : ECX +/- bevacizumab perioperative).
Tyrosin kinase inhibitors which inhibit VEGF receptors and EGFR are also investigated in gastric cancer with promising efficacy. Pazopanib, an orally available tyrosine kinase inhibitor, selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which results in inhibition of angiogenesis in tumors in which these receptors are upregulated. Pazopanib has the advantage of being an orally available anti-angiogenesis component.
Pazopanib shows promising activity in phase-II trials in renal cell cancer, breast cancer, soft tissue sarcoma and non small cell lung cancer. A phase-III trial of pazopanib in renal cell cancer (NCT00334282) is completed and resulted in the approval of Pazopanib for this disease. A phase-III trial in soft tissue sarcoma (NCT00753688) is currently performed.
In phase-I trials, pazopanib was investigated in combination with FOLFOX and Capecitabine/Oxaliplatin. FOLFOX could be administered in full dose with 800 mg pazopanib. In Cape/Ox, capecitabine had to be reduced to 850mg/m² bd.
5-FU- and oxaliplatin-based regimens are one of the established treatment standards for 1st-line therapy in metastatic gastric cancer. The efficacy of 5-FU, leukovorin and oxaliplatin (FLO) compared to 5-FU, cisplatin could be confirmed in a randomized phase-III trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). FLO has a favorable toxicity profile. In Germany, FLO is a widely used combination for advanced gastric cancer and is a recommended regimen in the new German S3-guidelines 2011.
The investigators therefore want to examine FLO + pazopanib.
- Conditions
- Advanced Gastric Cancer
- Being tested
- Pazopanib, 5-FU, Oxaliplatin, Leukovorin (FLO)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Adding Pazopanib to a standard chemotherapy consisting of FLO. 800 mg (2x400mg or 4x200mg) Pazopanib per day should be taken orally without food at least one hour before or two hours after a meal. Pazopanib will be given d1-14 each cycle (2 weeks cycles) with 12 cycles of chemotherapy FLO (d 1, each cycle). After 12 cycles chemotherapy FLO will be discontinued and Pazopanib will be given alone until disease progression
5-FU, Oxaliplatin, Leukovorin (FLO)Drug
Oxaliplatin 85 mg/m2 2h iv Leucovorin 200mg/m2 2h - iv FU 2600mg/m2 24h iv q2w for 12 cycles
| Study group | Role | What they receive |
|---|---|---|
| Arm A: FLO + Pazopanib | Experimental | Not described Receives: Drug: Pazopanib; Drug: 5-FU, Oxaliplatin, Leukovorin (FLO) |
| Arm B: FLO | Active comparator | Not described Receives: Drug: 5-FU, Oxaliplatin, Leukovorin (FLO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival rate at 6 months
Measured: 6 months after study entry
Secondary outcomes (9)
progression-free survival rate at 9 and 12 months
Measured: 9 and 12 months after study entry
median progression-free survival
Measured: 48 months
response rate
Measured: 48 months
duration of response
Measured: 48 months
toxicity
number of patients with Adverse Events according to CTC-criteria
Measured: 48 months
tolerability
number of patients having adverse events and require interruptions and dose reductions of chemotherapy
Measured: 48 months
overall survival
Measured: 48 months
time to treatment failure
Measured: 48 months
evaluation of the predictive and prognostic relevance of biomarkers
collection of plasma samples at designated time points during treatment and measuring of angiogenic factors correlating with response rate and outcome
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2012 (estimated)
- Study startNov 2011
- Primary completion14 Dec 2017
- Study completion14 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Advanced Gastric CancerStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, P. C. Thuss-Patience, Charite University, Berlin, Germany
- Investigators
- Peter Thuss-Patience, MD, Study chair, Charite University medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01503372
- Sponsor's protocol ID
- PaFLO
- Other IDs
- 2010-024379-15
- Acronym
- PaFLO
- Status last verified
- Feb 2019
- First submitted
- 22 Dec 2011
- Last updated
- 12 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Shah MA, Ramanathan RK, Ilson DH, Levnor A, D'Adamo D, O'Reilly E, Tse A, Trocola R, Schwartz L, Capanu M, Schwartz GK, Kelsen DP. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2006 Nov 20;24(33):5201-6. doi: 10.1200/JCO.2006.08.0887.
PubMed 17114652El-Rayes BF, Patel B, Zalupski M, et al. A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and GEJ cancer. ASCO Meeting Abstracts. 2009;27(15S):4563.
Li J, Kortmansky JS, Saif M, et al. Phase II study of mFOLFOX6 with bevacizumab (Bev) in metastatic gastric and esophageal (GE) adenocarcinoma. ASCO Meeting Abstracts. 2010;28(15_suppl):TPS203.
Enzinger PC, Ryan DP, Regan EM, et al. Phase II trial of docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer. ASCO Meeting Abstracts. 2008;26(15_suppl):4552.
Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson AB 3rd. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol. 2010 Jun 20;28(18):2947-51. doi: 10.1200/JCO.2009.27.7988. Epub 2010 May 10.
PubMed 20458043Moehler MH, Hartmann JT, Lordick F, et al. An open-label, multicenter phase II trial of sunitinib for patients with chemorefractory metastatic gastric cancer. ASCO Meeting Abstracts. 2010;28(15_suppl):e14503.
Hutson TE, Davis ID, Machiels JP, et al. Pazopanib (GW786034) is active in metastatic renal cell carcinoma (RCC): Interim results of a phase II randomized discontinuation trial (RDT). ASCO Meeting Abstracts. 2007;25(18_suppl):5031.
Slamon D, Gomez HL, Kabbinavar FF, et al. Randomized study of pazopanib + lapatinib vs. lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer. ASCO Meeting Abstracts. 2008;26(15_suppl):1016.
Sleijfer S, Papai Z, Le Cesne A, et al. Phase II study of pazopanib (GW786034) in patients (pts) with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043. ASCO Meeting Abstracts. 2007;25(18_suppl):10031.
Altorki N, Guarino M, Lee P, et al. Preoperative treatment with pazopanib (GW786034), a multikinase angiogenesis inhibitor in early-stage non-small cell lung cancer (NSCLC): A proof-of-concept phase II study. ASCO Meeting Abstracts. 2008;26(15_suppl):7557.
Brady J, Middleton M, Midgley RS, et al. A phase I study of pazopanib in combination with FOLFOX 6 or capeOx in subjects with colorectal cancer. ASCO Meeting Abstracts. 2009;27(15S):4133.
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. doi: 10.1056/NEJMoa073149.
PubMed 18172173Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jager E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. doi: 10.1200/JCO.2007.13.9378.
PubMed 18349393Moehler M, Al-Batran SE, Andus T, Anthuber M, Arends J, Arnold D, Aust D, Baier P, Baretton G, Bernhardt J, Boeing H, Bohle E, Bokemeyer C, Bornschein J, Budach W, Burmester E, Caca K, Diemer WA, Dietrich CF, Ebert M, Eickhoff A, Ell C, Fahlke J, Feussner H, Fietkau R, Fischbach W, Fleig W, Flentje M, Gabbert HE, Galle PR, Geissler M, Gockel I, Graeven U, Grenacher L, Gross S, Hartmann JT, Heike M, Heinemann V, Herbst B, Herrmann T, Hocht S, Hofheinz RD, Hofler H, Hohler T, Holscher AH, Horneber M, Hubner J, Izbicki JR, Jakobs R, Jenssen C, Kanzler S, Keller M, Kiesslich R, Klautke G, Korber J, Krause BJ, Kuhn C, Kullmann F, Lang H, Link H, Lordick F, Ludwig K, Lutz M, Mahlberg R, Malfertheiner P, Merkel S, Messmann H, Meyer HJ, Monig S, Piso P, Pistorius S, Porschen R, Rabenstein T, Reichardt P, Ridwelski K, Rocken C, Roetzer I, Rohr P, Schepp W, Schlag PM, Schmid RM, Schmidberger H, Schmiegel WH, Schmoll HJ, Schuch G, Schuhmacher C, Schutte K, Schwenk W, Selgrad M, Sendler A, Seraphin J, Seufferlein T, Stahl M, Stein H, Stoll C, Stuschke M, Tannapfel A, Tholen R, Thuss-Patience P, Treml K, Vanhoefer U, Vieth M, Vogelsang H, Wagner D, Wedding U, Weimann A, Wilke H, Wittekind C; AWMF; AWMF. [German S3-guideline "Diagnosis and treatment of esophagogastric cancer"]. Z Gastroenterol. 2011 Apr;49(4):461-531. doi: 10.1055/s-0031-1273201. Epub 2011 Apr 7. No abstract available. German.
PubMed 21476183Hogner A, Al-Batran SE, Siveke JT, Lorenz M, Bartels P, Breithaupt K, Malfertheiner P, Homann N, Stein A, Glaser D, Tamm I, Hinke A, Vogel A, Thuss-Patience P; PaFLO investigators. Pazopanib with 5-FU and oxaliplatin as first line therapy in advanced gastric cancer: A randomized phase-II study-The PaFLO trial. A study of the Arbeitsgemeinschaft Internistische Onkologie AIO-STO-0510. Int J Cancer. 2022 Mar 15;150(6):1007-1017. doi: 10.1002/ijc.33864. Epub 2021 Nov 15.
PubMed 34741530
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pazopanib With 5-Fluorouracil, Leucovorin and Oxaliplatin (FLO) as 1st-line Treatment in Advanced Gastric Cancer; a Randomized Phase-II-study of the Arbeitsgemeinschaft Internistische Onkologie
- ClinicalTrials.gov ID
- NCT01503372
- Acronym / sponsor ID
- PaFLO / PaFLO
- Conditions
- Advanced Gastric Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- 14 Dec 2017 (actual)
- Study completion
- 14 Dec 2017 (actual)
- First posted
- 4 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The prognosis of advanced gastric cancer and adenocarcinoma of the gastro-esophageal (GE) junction is poor. Even with modern chemotherapy the median survival ranges around 8-10 months.
Inhibition of neoangiogenesis seems to be a very promising approach in gastric cancer.
Vascular endothelial growth factor (VEGF) acts as one of the most potent stimulating agents of angiogenesis, and several strategies targeting the VEGF signaling pathway have been developed, including anti-VEGF antibodies, soluble receptors binding directly to VEGF ligand, anti-VEGF receptor (VEGFR) antibodies and VEGFR tyrosine kinase inhibitors. The breakthrough in the clinical development of anti-angiogenic therapy against colorectal cancer came in 2003 with a large prospective, randomized clinical trial of bevacizumab, a monoclonal antibody directed against VEGF. Anti-angiogenic therapy has introduced a highly effective, completely new mode of action in this area and is the new standard of care in advanced colorectal cancer.
The concept of VEGF inhibition is also very promising in gastric cancer. Bevacizumab was investigated in combination with irinotecan and cisplatin in a phase-II trial, including 47 patients with gastric and GE-junction carcinoma. Bevacizumab could safely be given and could improve time to tumor progression by 75% compared to historical controls. Several phase-II trials confirm the tolerability and promising efficacy of bevacizumab in gastric cancer (Bevacizumab + Docetaxel/Oxaliplatin; FOLFOX + Bevacizumab; Docetaxel/Cisplatin/Irinotecan + Bevacizumab). These results were so promising that randomized phase-III trials in the 1st-line and perioperative setting are under way (AVAGAST-trial: Cisplatin /Capecitabine +/- bevacizumab 1st line ; MAGIC-B-trial : ECX +/- bevacizumab perioperative).
Tyrosin kinase inhibitors which inhibit VEGF receptors and EGFR are also investigated in gastric cancer with promising efficacy. Pazopanib, an orally available tyrosine kinase inhibitor, selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which results in inhibition of angiogenesis in tumors in which these receptors are upregulated. Pazopanib has the advantage of being an orally available anti-angiogenesis component.
Pazopanib shows promising activity in phase-II trials in renal cell cancer, breast cancer, soft tissue sarcoma and non small cell lung cancer. A phase-III trial of pazopanib in renal cell cancer (NCT00334282) is completed and resulted in the approval of Pazopanib for this disease. A phase-III trial in soft tissue sarcoma (NCT00753688) is currently performed.
In phase-I trials, pazopanib was investigated in combination with FOLFOX and Capecitabine/Oxaliplatin. FOLFOX could be administered in full dose with 800 mg pazopanib. In Cape/Ox, capecitabine had to be reduced to 850mg/m² bd.
5-FU- and oxaliplatin-based regimens are one of the established treatment standards for 1st-line therapy in metastatic gastric cancer. The efficacy of 5-FU, leukovorin and oxaliplatin (FLO) compared to 5-FU, cisplatin could be confirmed in a randomized phase-III trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). FLO has a favorable toxicity profile. In Germany, FLO is a widely used combination for advanced gastric cancer and is a recommended regimen in the new German S3-guidelines 2011.
The investigators therefore want to examine FLO + pazopanib.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: FLO + Pazopanib | Experimental | Drug: Pazopanib, Drug: 5-FU, Oxaliplatin, Leukovorin (FLO) |
| Arm B: FLO | Active comparator | Drug: 5-FU, Oxaliplatin, Leukovorin (FLO) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.
- Age ≥ 18 years.
- Histologically confirmed adenocarcinoma of the stomach or the gastroesophageal junction with either metastatic or locally advanced disease, incurable by operation.
- Eastern Cooperative Oncology Group (ECOG) performance status of < or = 2
- At least one unidimensional, measurable tumor parameter (according to RECIST 1.1)
Key exclusion criteria (25 listed)
- Prior malignancy, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix.
- Overexpression of HER-2, defined as IHC 3+ or IHC 2+ and FISH positive.
- Known hypersensitivity against 5-FU, leukovorin, oxaliplatin or other platinum compounds or pazopanib.
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or the absorption of investigational product
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibAdding Pazopanib to a standard chemotherapy consisting of FLO. 800 mg (2x400mg or 4x200mg) Pazopanib per day should be taken orally without food at least one hour before or two hours after a meal. Pazopanib will be given d1-14 each cycle (2 weeks cycles) with 12 cycles of chemotherapy FLO (d 1, each cycle). After 12 cycles chemotherapy FLO will be discontinued and Pazopanib will be given alone until disease progression | Drug | Arm A: FLO + Pazopanib |
| 5-FU, Oxaliplatin, Leukovorin (FLO)Oxaliplatin 85 mg/m2 2h iv Leucovorin 200mg/m2 2h - iv FU 2600mg/m2 24h iv q2w for 12 cycles | Drug | Arm A: FLO + Pazopanib, Arm B: FLO |
Primary outcome
progression-free survival rate at 6 months
Time frame: 6 months after study entry
9 secondary outcomes
progression-free survival rate at 9 and 12 months
Time frame: 9 and 12 months after study entry
median progression-free survival
Time frame: 48 months
response rate
Time frame: 48 months
duration of response
Time frame: 48 months
toxicity
Time frame: 48 months
tolerability
Time frame: 48 months
overall survival
Time frame: 48 months
time to treatment failure
Time frame: 48 months
evaluation of the predictive and prognostic relevance of biomarkers
Time frame: 48 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Background: PubMed 17114652Shah MA, Ramanathan RK, Ilson DH, Levnor A, D'Adamo D, O'Reilly E, Tse A, Trocola R, Schwartz L, Capanu M, Schwartz GK, Kelsen DP. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2006 Nov 20;24(33):5201-6. doi: 10.1200/JCO.2006.08.0887.
- BackgroundEl-Rayes BF, Patel B, Zalupski M, et al. A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and GEJ cancer. ASCO Meeting Abstracts. 2009;27(15S):4563.
- BackgroundLi J, Kortmansky JS, Saif M, et al. Phase II study of mFOLFOX6 with bevacizumab (Bev) in metastatic gastric and esophageal (GE) adenocarcinoma. ASCO Meeting Abstracts. 2010;28(15_suppl):TPS203.
- BackgroundEnzinger PC, Ryan DP, Regan EM, et al. Phase II trial of docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer. ASCO Meeting Abstracts. 2008;26(15_suppl):4552.
- Background: PubMed 20458043Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson AB 3rd. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol. 2010 Jun 20;28(18):2947-51. doi: 10.1200/JCO.2009.27.7988. Epub 2010 May 10.
- BackgroundMoehler MH, Hartmann JT, Lordick F, et al. An open-label, multicenter phase II trial of sunitinib for patients with chemorefractory metastatic gastric cancer. ASCO Meeting Abstracts. 2010;28(15_suppl):e14503.
- BackgroundHutson TE, Davis ID, Machiels JP, et al. Pazopanib (GW786034) is active in metastatic renal cell carcinoma (RCC): Interim results of a phase II randomized discontinuation trial (RDT). ASCO Meeting Abstracts. 2007;25(18_suppl):5031.
- BackgroundSlamon D, Gomez HL, Kabbinavar FF, et al. Randomized study of pazopanib + lapatinib vs. lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer. ASCO Meeting Abstracts. 2008;26(15_suppl):1016.
- BackgroundSleijfer S, Papai Z, Le Cesne A, et al. Phase II study of pazopanib (GW786034) in patients (pts) with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043. ASCO Meeting Abstracts. 2007;25(18_suppl):10031.
- BackgroundAltorki N, Guarino M, Lee P, et al. Preoperative treatment with pazopanib (GW786034), a multikinase angiogenesis inhibitor in early-stage non-small cell lung cancer (NSCLC): A proof-of-concept phase II study. ASCO Meeting Abstracts. 2008;26(15_suppl):7557.
- BackgroundBrady J, Middleton M, Midgley RS, et al. A phase I study of pazopanib in combination with FOLFOX 6 or capeOx in subjects with colorectal cancer. ASCO Meeting Abstracts. 2009;27(15S):4133.
- Background: PubMed 18172173Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. doi: 10.1056/NEJMoa073149.
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At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1
A Phase I Study of CG-7321 Monotherapy or Combination Therapy in Advanced Solid Tumors
Advanced Solid Tumors, Breast Cancer
Active, not recruitingPhase 2
Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma
MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer
RecruitingPhase 1
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Solid Tumor, Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Thuss-Patience, MD study chair
Charite University medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pazopanib and 5-FU, Oxaliplatin, Leukovorin (FLO) in people with Advanced Gastric Cancer, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival rate at 6 months (time frame: 6 months after study entry). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01503372, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.