A Study of Abemaciclib and Cabozantinib in People With Clear Cell Renal Cell Carcinoma (ccRCC)

Introduction

• Org Study ID: 24-126
• NTC ID: NCT06835972
• Lead Sponsor Name: Memorial Sloan Kettering Cancer Center
• Status: RECRUITING

Conditions

• Clear Cell Renal Cell Carcinoma

Brief Summary

The researchers are doing this study to find out whether the combination of abemaciclib and cabozantinib is a safe and effective treatment for people with metastatic clear cell renal cell carcinoma (ccRCC). The researchers will test different doses of the study drugs to find the highest doses that cause few or mild side effects in participants.

Eligibility Criteria

Inclusion Criteria:

* Age ≥ 18 years at the time of informed consent
* Patient must be able to provide informed consent, or a legal authorized representative (LAR) must be identified to provide consent in cases where the patient cannot
* Signed and dated IRB-approved Informed Consent Form
* Patient must have a histologically confirmed diagnosis of metastatic stage IV clear cell renal cell carcinoma.
* Patient should have availability of archival tissue that enables definitive diagnosis of ccRCC, per review at participating site, accompanied by an associated pathology report. Specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion. NOTE: If archival tissue is unavailable, a patient can still enroll onto the study with documented confirmation from the study PI.
* Patients must have at least one extra-skeletal, extracranial measurable lesion as defined by RECIST v1.1 7. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Patients must have progressed on at least 2 prior lines of systemic therapy and a maximum of 3 prior lines of systemic therapy in the metastatic setting
* Patient must have progressed on 1 prior PD-1 or PD-L1 targeted treatment and prior VEGFR directed TKI therapy
* Patients must have recovered to baseline or < Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events (AEs) are clinically non-significant and/or stable on supportive therapy (See Appendix 2)
* Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and registration.
* The patient can swallow oral medications.
* Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
* ANC ≥ 1500 cells/μL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
* WBC counts ≥ 2500/μL and ≤ 15,000/μL without G-CSF
* Absolute Lymphocyte count 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
* Significant arterial disease (e.g., stroke, transient ischemic attack, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.
* Corrected QT interval calculated by the Fridericia formula (QTcF) > 470 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.

Note: If a single ECG shows a QTcF with an absolute value > 470 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility

* Concomitant anticoagulation with coumadin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:

* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 6 weeks before first dose of study treatment. Completeness of wound healing from any surgery must be ascertained. There must be a minimum of two weeks from completion of wound healing to start of study.
* Evidence of tumor invading the gastrointestinal tract, active peptic ulcer disease, active inflammatory bowel disease, active diverticulitis, active cholecystitis, symptomatic/active cholangitis or appendicitis, acute pancreatitis, acute obstruction of pancreatic duct or common bile duct, or active gastric outlet obstruction.
* Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.
* Patients with a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment.
* The patient has tumor invading or encasing any major blood vessels, with exception of renal vessels ipsilateral to the primary renal tumor.
* The patient has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus) at time of study screening.
* Patients with malabsorption syndrome.
* Patients with a serious non-healing wound/ulcer/bone fracture.
* Patients with active COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to first dose of study treatment.
* Previously identified allergy or hypersensitivity to components of the study treatment formulations.
* Radiation therapy for bone metastasis within 2 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
* The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).