Maintenance Zanzalintinib With Etoposide After HDCT in GCT

Recruiting now · Phase 1/Phase 2

Conditions studied: Germ Cell Tumor

In brief

This is an open label, single arm phase I/II trial of maintenance zanzalintinib in combination with oral etoposide in patients with relapsed GCT treated with HDCT and PBSCT with a safety lead-in cohort in patients with relapsed, refractory metastatic GCT.

Key facts

Study ID

NCT06937866

Run by

Indiana University

People needed

38

Starts

2025-11-12

Expected to finish

2031-09-01

Last updated by the study team

2025-11-21

Who can join

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

You may qualify if…

• Phase I:
• Histological or serological evidence of incurable, refractory or relapsed metastatic germ cell tumor, including seminoma, non-seminoma, and women with ovarian GCTs.
• Must have received initial cisplatin-based combination chemotherapy AND demonstrated progression following at least one salvage regimen for advanced germ-cell neoplasm and now considered incurable with standard therapies, including further chemotherapy or surgery.
• 1. "Failure" of prior therapy is defined as: 2.1.1.A >25% increase in the products of the perpendicular diameters of measurable tumor masses during prior therapy which are not amenable to surgical resection.
• 1.2.The presence of new tumors that are not amenable to surgical resection 2.1.3.An increase in AFP or beta-hcg (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of failure).
• NOTE: Patients with clinically growing teratoma (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery.
• Subjects with relapsed primary mediastinal non-seminomatous germ-cell tumor (PMNSGCT) or late relapse (>2 years) not amenable to resection are eligible if they have received first line platinum-based chemotherapy and are deemed not amenable to surgical resection.
• Phase II:
• Histological or serological evidence of non-seminomatous GCT
• Relapsed disease after first-line cisplatin-based combination chemotherapy
• Completed salvage treatment with HDCT and PBSCT for 2 tandem cycles per Institutional Guidelines
• HDCT must have been used as the initial salvage chemotherapy regimen (2nd line therapy) 4.1. Note: 1 or 2 cycles of standard course regimens prior to HDCT are acceptable (regimens including VeIP [vinblastine+ifosfamide+cisplatin] or TIP [paclitaxel+ifosfamide+cisplatin] or PVB [cisplatin+vinblastine+bleomycin]
• Normal or declining tumor markers (AFP and hCG) at time of screening per discretion of treating physician. Patients need to be considered disease free with no known active residual GCT.
• Last dose of HDCT must be ≤ 16 weeks from study registration
• Women with ovarian germ cell tumors are eligible
• For All Patients:
• Written informed consent and HIPAA authorization for release of personal health information.
• Capable of understanding and complying with the protocol requirements.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 28 days of study registration
• Adverse events from prior therapy recovered to CTCAE v5.0 grade ≤ 2 at time of registration unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid).
• Adequate laboratory values obtained within 14 days prior to registration for protocol therapy and as defined below:
• 1. Hemoglobin ≥ 9g/dL 6.2. WBC ≥ 2500/µL 6.3. Absolute neutrophil count ≥ 1500/mm3 6.4. Platelet count ≥ 100,000/mm3 6.5. Total bilirubin ≤ 1.5 X ULN except patients with documented Gilbert's syndrome (≤ 3 X ULN) 6.6. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤3 X ULN; for patients with hepatic metastases, ALT and AST ≤ 5 X ULN. For subjects with documented bone metastasis ALP ≤ 5 X ULN. 6.7. Serum albumin ≥ 2.8g/dL 6.8. (PT)/INR or partial thromboplastin time (PTT) test ≤ 1.5 x upper limit of normal and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN). 6.9. Calculated creatinine clearance
• ≥ 50 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation. 6.10. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine.
• Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Appendix II) during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.

You may not qualify if…

• Phase I:
• Patients who have not received greater than or equal to 1 salvage treatment regimens or have further potentially curative treatment options.
• Phase II:
• Relapsed pure seminoma
• Rising tumor markers (AFP and hCG) at time of screening per discretion of treating physician
• Patients who completed 2nd cycle of HDCT (time since last dose of HDCT) > 16 weeks ago
• For All Patients:
• Prior treatment with zanzalintinib
• Receipt of any type of cytotoxic, small molecule kinase inhibitor, biologic, investigational, or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 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.
• Prior hypersensitivity to etoposide which did not recover with supportive care
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
• 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.
• Prior active malignancy is NOT allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast, or prostate cancer, superficial bladder cancer, Gleason < Grade 7 and ≤ T2N0M0 prostate cancers, or other cancer for which the subject has been disease-free for at least three years or at discretion of treating physician.
• History of psychiatric illness or social situations that would limit compliance with study requirements.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• 1. Unstable or deteriorating cardiovascular disorders: 9.1.1. Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes), unstable or deteriorating cardiovascular disorders.
• 1.2. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• 1.3. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• 2. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment. Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and 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. Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.
• 3. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: 9.3.1. Tumors invading the GI-tract from external viscera 9.3.2. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis 9.3.3. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before the first dose unless cause of obstruction is definitively managed and subject is asymptomatic 9.3.4. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• 3.5. Known gastric or esophageal varices 9.3.6. Ascites, pleural effusion, or pericardial fluid requiring drainage in the last 4 weeks.

Where it is running

• Indiana University Melvin and Bren Simon Comprehensive Cancer Center — Indianapolis, Indiana, United States (enrolling)

Full record on ClinicalTrials.gov

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