Maintenance Zanzalintinib With Etoposide After HDCT in GCT

NCT06937866 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0894
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Germ Cell Tumor

Keywords

zanzalintinib; maintenance chemotherapy

Outcome Measures

Primary Outcomes (3)

• Phase 1: Rate of hematologic toxicity

  Rate of hematologic toxicity including neutropenia, anemia, or thrombocytopenia requiring intervention (transfusions or antibiotics)

  28 days

• Phase 1: Rate of non-hematologic toxicity

  Rate of non-hematologic toxicity

  28 days

• Phase II: 12-month Progression Free Survival

  12-month PFS based on investigator determination of tumor progression (clinical, radiographic, and/or tumor markers including AFP and hCG)

  12 months

Secondary Outcomes (2)

• Phase II: 12-month Overall Survival (OS)

  12 months post time of registration

• Phase II: Incidence of Adverse Events

  Start of treatment until end of treatment safety assessments (up to 2 years)

Study Arms (2)

Phase 1 Dose Escalation

EXPERIMENTAL

Drug: Zanzalintinib; Drug: Etoposide Capsule

Phase II Dose Expansion

EXPERIMENTAL

Patients will be added at highest zanzalintinib dose tolerated, 40mg or 60mg.

Drug: Zanzalintinib; Drug: Etoposide Capsule

Interventions

Zanzalintinib DRUG

Two zanzalintinib doses of 40mg and 60mg. The initial starting dose of zanzalintinib will be 40mg. The patients will receive zanzalintinib orally daily continuously for 28 day cycles.

Phase 1 Dose Escalation; Phase II Dose Expansion

Etoposide Capsule DRUG

Oral daily for 21 days of each 28 day cycle.

Phase 1 Dose Escalation; Phase II Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• "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.
• 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

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).

Sponsors & Collaborators

• Indiana University: lead
• Exelixis: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Jennifer King, MD

  Indiana University Simon Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer King, MD

CONTACT

317-948-0361; jmstrass@iu.edu

Christin Snow, RN

CONTACT

317-274-5830; chsnow@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: April 22, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): September 1, 2031
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

US (1)