Phase I/II Eval Safety & Prelim Activity Nivolumab Comb W/Vorolanib Pts W/Refractory Thoracic Tumors

Completed · Phase 1/Phase 2

Conditions studied: Thymic Carcinoma, Non-small Cell Lung Cancer, Refractory Thoracic Tumors, Small-Cell Lung Cancer

In brief

This is a two-agent, open-label, non-randomized, Phase 1/2 dose escalation and dose expansion study of combinatorial oral vorolanib plus infusional nivolumab in patients with Non-Small Cell Lung Cancer naïve to checkpoint inhibitor therapy, Non-Small Cell Lung Cancer who have progressed on checkpoint inhibitor therapy, Small Cell Lung Cancer ( who have progressed on platinum-based chemotherapy, and thymic carcinoma.

Key facts

Study ID

NCT03583086

Run by

Vanderbilt-Ingram Cancer Center

People needed

88

Starts

2018-07-10

Expected to finish

2024-04-27

Last updated by the study team

2024-10-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed and dated written informed consent.
• Male or female ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Having progressed on at least one prior line of therapy, or refused chemotherapy, histologically or cytologically confirmed diagnosis of one of the following:
• Dose Escalation and Expansion Cohorts:
• Checkpoint Inhibitor Naïve Non-Small Cell Lung Cancer patients must have progressed on front-line cytotoxic chemotherapy or have refused chemotherapy and may have received up to three prior treatment regimens for stage IV disease provided no regimens included an anti-PD1 or PD-L1 agent or an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.
• Progressed on Checkpoint Inhibitor Non-Small Cell Lung Cancer patients must have progressed on front-line or second checkpoint inhibitor therapy and may have received up to three prior treatment regimens for stage IV disease provided no regimens included an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.
• Patients with EGFR, ALK, ROS1 and BRAF NSCLC must have progressed on an oral TKI and may have received an unlimited number of prior regimens.
• Thymic carcinoma patients must not be eligible for surgical resection at the time of enrollment and may have received any number of prior lines of therapy provided no regimens included an anti-PD1 or PD-L1 agent or an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.
• Small Cell Lung Cancer patients must have progressed on platinum-based chemotherapy and may have received up to three prior lines of therapy for stage IV disease provided no prior regimen included an oral VEGF TKI; prior regimens can include an anti-PD-1 or PD-L1 agent.
• At least one measureable lesion as defined by RECIST 1.1 which can be followed by CT or MRI.
• Adequate organ function prior to first dose of protocol-indicated treatment, including:
• Absolute neutrophil count (ANC) ≥ 1,500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5 times institutional upper limit of normal (ULN), or calculated creatinine clearance ≥ 40 mL/min (per the Cockcroft-Gault formula)
• Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who must have total bilirubin < 3.0 mg/dL)
• Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x ULN, (≤ 5.0 x ULN with documented liver metastases)
• Women must not be breastfeeding.
• Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment.
• Women of childbearing potential is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal.
• Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes.
• If menopausal status is considered for the purpose of evaluating childbearing potential, women < 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential.
• Women of childbearing potential must agree to follow instructions for acceptable contraception Appendix 5 from the time of signing consent, and for 23 weeks after their last dose of protocol-indicated treatment.
• Men not azoospermic who are sexually active with women of childbearing potential must agree to follow instructions for acceptable contraception (Appendix 5), from the time of signing consent, and for 31 weeks after their last dose of protocol-indicated treatment.

You may not qualify if…

• ≤ 28 days before first dose of protocol-indicated treatment:
• Anti-cancer treatment with bevacizumab.
• Major surgery requiring general anesthesia or significant traumatic injury.
• ≤ 14 days before first dose of protocol-indicated treatment:
• Anti-cancer therapy with an approved or investigational agent (including chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or biological therapy).
• Radiosurgery or radiotherapy. (Note: A tumor lesion situated in a previously irradiated area is considered a measureable/target lesion only if subsequent disease progression has been documented in the lesion.)
• Initiation of a new erythropoietin, darbepoietin, and/or bisphosphonate therapy. (See Section 9.3.)
• Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery.)
• Serious or uncontrolled infection.
• Infection requiring parenteral antibiotics. (Note: Patients with a non-serious infection under active treatment and controlled with oral antibiotics initiated at least 10 days prior to initiation of protocol-indicated treatment are not excluded - e.g. urinary tract infection controlled with oral antibiotics.)
• Unexplained fever > 38.0 ºC.
• ≤ 7 days before first dose of protocol-indicated treatment:
• Receipt of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF). (See Section 9.3.)
• Concurrent use of any medications or substances (e.g. herbal supplement or food) known to be a strong inhibitor or strong inducer of CYP3A4.
• Although corticosteroids are considered to be strong inducers of CYP3A4, physiologic replacement doses of corticosteroids ≤ 10 mg daily prednisone or equivalent are allowed (Section 9).
• Inadequate recovery from toxicity attributed to prior anti-cancer therapy.
• With the exception of alopecia, fatigue, or peripheral neuropathy, patients must have recovered to ≤ Grade 1 (NCI-CTCAE v5.0) residual toxicity prior to first dose of protocol-indicated treatment.
• Patients requiring replacement therapy (e.g. prednisone or thyroid replacement therapy) for endocrine disorders from prior checkpoint inhibitor therapy are allowed
• Known history of allergy or intolerance which, in the opinion of the investigator, was an unacceptable adverse reaction attributed by the investigator to any prior anti-neoplastic therapy specifically targeting vascular endothelial growth factor or the VEGF receptor.
• Known history of allergy or intolerance which, in the opinion of the investigator, was an unacceptable adverse reaction attributed by the investigator to any prior anti-neoplastic therapy specifically targeting T-cell costimulation or immune checkpoint pathways - i.e. nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), atezolizumab (TECENTRIQ), ipilimumab (YERVOY), etc.
• Non-healing wounds on any part of the body.
• Known or suspected clinically significant active bleeding.
• Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug - e.g. Crohn's disease, ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day), malabsorption, or bowel obstruction.
• patients with radiographic evidence of major airway or blood vessel invasion by cancer, radiographic evidence of intra-tumor cavitation, or gross hemoptysis (≥ one teaspoon) within the preceding 2 months.
• Significant cardiovascular disease or condition including:

Where it is running

• Stanford Cancer Institute — Palo Alto, California, United States
• Winship Cancer Institute, Emory University — Atlanta, Georgia, United States
• University of Chicago Medical Center — Chicago, Illinois, United States
• Providence Cancer Institute Franz Clinic — Portland, Oregon, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• Baptist Clinical Research Institute — Memphis, Tennessee, United States
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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