RECRUITING

Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus

Conditions

Renal Cancer Kidney Cancer Renal Cell Carcinoma Inferior Vena Cava Thrombosis

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The primary objective of this study is to evaluate whether the combination of Pembrolizumab and Axitinib given in the neoadjuvant setting can change the Inferior Vena Cava Tumor Thrombus burden. A decrease in the size of the tumor thrombus can potentially lead to decrease in surgical complications, improve patient related health outcomes, and improve long term outcomes such as progression free survival and overall survival.

Official Title

Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma with Associated Inferior Vena Cava Tumor Thrombus (NEOPAX)

Quick Facts

Study Start:2023-12-04

Study Completion:2029-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05969496

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Provision to sign and date the consent form. * Stated willingness to comply with all study procedures and be available for the duration of the study. * Participant self-identified gender ages \>/= 18 years old is acceptable and appropriate if they meet other inclusion criteria. * Histologically proven clear cell component RCC. * An upfront candidate for definitive surgery per treating Urologist. * Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative intent) per treating urologist. * T Stage of any of the following: cT3b, cT3c, cT4 * N stage of any of the following: cN0 or cN1 * M stage of any of the following: cM0 or cM1 * ECOG performance status 0 - 2. * Urinalysis \<2+ protein. If dipstick is ≥2+ then a 24-hour urine collection should be performed, and the patient may enter the trial if urinary protein is \<2g per 24 hours. * All participants who have reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment. * Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy * For males with reproductive potential, use effective birth control during treatment with Axitinib and Pembrolizumab is recommended.	* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to enrollment. * Has had major surgery within 4 weeks or received radiation therapy within 1 week prior to enrollment to the study. * Has had prior treatment with any anti-programmed cell death (anti-PD-1) or programmed cell death ligand 1 (PD-L1), or an antibody targeting any other immune-regulatory receptors or mechanisms. * Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR). * Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to Axitinib. * Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy greater than Prednisone 10 mg daily or a steroid equivalent, or any other form of immunosuppressive therapy within 7 days prior to enrollment to the study except in the case of central nervous system (CNS) metastases. * Has an active autoimmune disease requiring systemic treatment within the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjogren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement are not excluded. * Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ, thyroid cancer (papillary, hurthle cell or follicular), or localized prostate cancer are acceptable if they have undergone potentially curative therapy. * Has known active CNS metastases and/or carcinomatous meningitis. * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * ALT or AST above 3 times the upper limit of normal * Has received a live virus vaccine within 30 days of enrollment to the study. * Active GI bleeding, as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy. * Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation. * Has QT interval corrected for heart rate (QTc) ≥480 msec. * Has a history of any of the following cardiovascular conditions within 12 months of enrollment to the study: * Myocardial infarction * Unstable angina pectoris * Cardiac angioplasty or stenting * Coronary/peripheral artery bypass graft * Class III or IV congestive heart failure per New York Heart Association * Cerebrovascular accident or transient ischemic attack * Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg on 3 or more dose optimized anti- hypertensive medication. * Has evidence of inadequate wound healing per treating physician discretion. * Has active bleeding disorder or other history of significant bleeding episodes within 30 days of enrollment to the study. * Has current use (within 7 days of enrollment) or anticipated need for treatment with drugs or foods that are known to be strong cytochrome P450 (CYP3A4/5) inhibitors. * Has current use (within 7 days of enrollment) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study by subject self-report. * Has had a prior solid organ transplant. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.

Inclusion Criteria

Exclusion Criteria

* Provision to sign and date the consent form.
* Stated willingness to comply with all study procedures and be available for the duration of the study.
* Participant self-identified gender ages \>/= 18 years old is acceptable and appropriate if they meet other inclusion criteria.
* Histologically proven clear cell component RCC.
* An upfront candidate for definitive surgery per treating Urologist.
* Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative intent) per treating urologist.
* T Stage of any of the following: cT3b, cT3c, cT4
* N stage of any of the following: cN0 or cN1
* M stage of any of the following: cM0 or cM1
* ECOG performance status 0 - 2.
* Urinalysis \<2+ protein. If dipstick is ≥2+ then a 24-hour urine collection should be performed, and the patient may enter the trial if urinary protein is \<2g per 24 hours.
* All participants who have reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment.
* Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
* Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy
* For males with reproductive potential, use effective birth control during treatment with Axitinib and Pembrolizumab is recommended.

* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to enrollment.
* Has had major surgery within 4 weeks or received radiation therapy within 1 week prior to enrollment to the study.
* Has had prior treatment with any anti-programmed cell death (anti-PD-1) or programmed cell death ligand 1 (PD-L1), or an antibody targeting any other immune-regulatory receptors or mechanisms.
* Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR).
* Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to Axitinib.
* Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy greater than Prednisone 10 mg daily or a steroid equivalent, or any other form of immunosuppressive therapy within 7 days prior to enrollment to the study except in the case of central nervous system (CNS) metastases.
* Has an active autoimmune disease requiring systemic treatment within the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjogren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement are not excluded.
* Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ, thyroid cancer (papillary, hurthle cell or follicular), or localized prostate cancer are acceptable if they have undergone potentially curative therapy.
* Has known active CNS metastases and/or carcinomatous meningitis.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* ALT or AST above 3 times the upper limit of normal
* Has received a live virus vaccine within 30 days of enrollment to the study.
* Active GI bleeding, as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
* Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation.
* Has QT interval corrected for heart rate (QTc) ≥480 msec.
* Has a history of any of the following cardiovascular conditions within 12 months of enrollment to the study:
* Myocardial infarction
* Unstable angina pectoris
* Cardiac angioplasty or stenting
* Coronary/peripheral artery bypass graft
* Class III or IV congestive heart failure per New York Heart Association
* Cerebrovascular accident or transient ischemic attack
* Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg on 3 or more dose optimized anti- hypertensive medication.
* Has evidence of inadequate wound healing per treating physician discretion.
* Has active bleeding disorder or other history of significant bleeding episodes within 30 days of enrollment to the study.
* Has current use (within 7 days of enrollment) or anticipated need for treatment with drugs or foods that are known to be strong cytochrome P450 (CYP3A4/5) inhibitors.
* Has current use (within 7 days of enrollment) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study by subject self-report.
* Has had a prior solid organ transplant.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.

Contacts and Locations

Study Contact

Matthew Lee

CONTACT

720-848-0630

matthew.lee@cuanscutz.edu

Principal Investigator

Elizabeth E Kessler, MD

PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Study Locations (Sites)

University of Colorado Cancer Center

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

Elizabeth E Kessler, MD, PRINCIPAL_INVESTIGATOR, University of Colorado, Denver

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-04

Study Completion Date2029-11

Study Record Updates

Study Start Date2023-12-04

Study Completion Date2029-11

Terms related to this study

Additional Relevant MeSH Terms

Renal Cancer
Kidney Cancer
Renal Cell Carcinoma
Inferior Vena Cava Thrombosis