Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
15 participants
INTERVENTIONAL
2017-11-29
2022-12-29
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Avelumab, Axitinib, Palbociclib
For the Phase 1:
Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle).
For the Phase 2:
Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.
Avelumab
A human antibody of the immunoglobulin gamma-1 isotype that specifically targets and blocks the Programmed Death ligand (PD-L1) for PD-1.
Axitinib
A selective oral (tablet) inhibitor of tyrosine kinases Vascular Endothelial Growth Factor (VEGF) receptors 1, 2, and 3. These receptors are implicated in pathologic angiogenesis, tumor growth and cancer progression.
Palbociclib
A selective, reversible oral (capsule) inhibitor of cyclin-dependent kinases (CDK) 4 and 6. The inhibition of CDK 4/6 blocks DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase.
Interventions
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Avelumab
A human antibody of the immunoglobulin gamma-1 isotype that specifically targets and blocks the Programmed Death ligand (PD-L1) for PD-1.
Axitinib
A selective oral (tablet) inhibitor of tyrosine kinases Vascular Endothelial Growth Factor (VEGF) receptors 1, 2, and 3. These receptors are implicated in pathologic angiogenesis, tumor growth and cancer progression.
Palbociclib
A selective, reversible oral (capsule) inhibitor of cyclin-dependent kinases (CDK) 4 and 6. The inhibition of CDK 4/6 blocks DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase.
Other Intervention Names
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Eligibility Criteria
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Exclusion Criteria
* For Phase 1 portion, \>2 lines of prior therapy in the metastatic setting.
* For the dose escalation phase of the study or until the MTD for the combination regimen has been determined, patients with moderate hepatic impairment defined as AST, ALT, alkaline phosphatase (ALP) \>5 times ULN, which would be grade 3 or higher. However, patients with liver metastases with AST/ALT ≤ 5 x ULN can be included in the study.
* For Phase 2 portion, any prior therapy in the metastatic setting.
Clinical criteria for phase 1 and phase 2 studies:
* Patients with treated brain metastases are eligible as are patients with new, active untreated brain metastasis.
* Participants with a history of myocardial infarction within the last 2 years or with significant cardiac arrhythmias uncontrolled by medication or pacemaker,
* Participants with any history of interstitial lung disease,
* Prior clinically significant toxicities from anticancer agents or radiotherapy which have not regressed to Grade ≤ 1 severity (NCI-CTCAE version 4.03) apart from peripheral neuropathy and alopecia,
* History of any second malignancy in the last two years; patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease-free for at least two years,
* Autoimmune condition requiring medical intervention,
* Uncontrolled concomitant illness, active infection requiring i.v. antibiotics,
* Patients who have had a thromboembolic event within six months are excluded, as are patients on anticoagulants, except for low dose aspirin (\<100 mg/day) and low doses of anticoagulants meant to keep line access open;
* Patients with Grade 3 or 4 (serious) gastrointestinal bleeding within the last six months are excluded.
* Prior \> G3 hemoptysis, major blood vessel involvement (specifically including aorta, superior and inferior vena cave, main pulmonary arteries and veins, subclavian arteries and veins and other large blood vessels that in the investigator's opinion places the patients at high risk for major bleeding), and/or central cavitations,
* Known or suspected drug hypersensitivity to any drug used in the combination,
* Difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the oral drugs,
* Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the investigator may affect the patient's ability to sign the informed consent and undergo study procedures,
* Taking another experimental drug within 28 days prior to day 1 of the protocol medications in this study,
* Pregnant or breast-feeding women,
* Both male and female patients of reproductive potential must agree to use highly effective contraception, during the study and for 3 months following the last dose of study drug,
* Patients currently taking strong CYP3A4 inducers and inhibitors,
* Patients currently taking proton pump inhibitors due to their impact on the disposition of palbociclib during the phase 1.
* Patients taking other anticancer agents with the exception of denosumab or equivalent medication for bone metastases.
* A time period of at least three weeks (including radiotherapy) or five drug half-lives, whichever is shorter must have elapsed from last non-investigational therapy before first day of treatment on this study,
* A time period of at least 10 days must have elapsed from last palliative radiotherapy before the first day of treatment on this study,
* IMMUNOSUPRESSANTS: Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
* AUTOIMMUNE DISEASE: Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
* ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation.
* INFECTIONS: Active infection requiring IV (Intra venous) therapy.
* HIV/AIDS: Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
* HEPATITIS: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
* VACCINATION: Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
* HYPERSENSITIVITY TO STUDY DRUG: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
* CARDIOVASCULAR DISEASE: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia inadequately controlled by medication.
* OTHER PERSISTING TOXICITIES: Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
* Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
18 Years
ALL
No
Sponsors
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ARC Foundation for Cancer Research
OTHER
Pfizer
INDUSTRY
Worldwide Innovative Network Association
OTHER
Responsible Party
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Principal Investigators
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RAZELLE KURZROCK, MD
Role: PRINCIPAL_INVESTIGATOR
Medical College of Wisconsin, Milwaukee, WI, USA
Locations
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UCSD Moores Cancer Center
La Jolla, California, United States
Avera Cancer Center
Sioux Falls, South Dakota, United States
Chaim Sheba Medical Center
Ramat Gan, , Israel
Centre Hospitalier Luxembourg
Luxembourg, , Luxembourg
Vall Hebron Institute of Oncology
Barcelona, , Spain
Countries
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References
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Solomon B, Callejo A, Bar J, Berchem G, Bazhenova L, Saintigny P, Wunder F, Raynaud J, Girard N, Lee JJ, Sulaiman R, Prouse B, Bresson C, Ventura H, Magidi S, Rubin E, Young B, Onn A, Leyland-Jones B, Schilsky RL, Lazar V, Felip E, Kurzrock R. A WIN Consortium phase I study exploring avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer. Cancer Med. 2022 Jul;11(14):2790-2800. doi: 10.1002/cam4.4635. Epub 2022 Mar 20.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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sponsor website
SIMS article link: A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer.
Link to the publication of the results of the Phase 1 part of the study
Other Identifiers
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2017-001455-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
WIN001
Identifier Type: -
Identifier Source: org_study_id