A Phase II Trial of Cabozantinib With Patients With Refractory GCTs

NCT04876456 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0752
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the CTO-IUSCCC-0752 study is to investigate the use of Cabozantinib for patients with incurable, refractory germ cell tumors. Patients will be treated until evidence of disease progression, non-compliance with study protocol, unacceptable major toxicity, at subject's own request for withdrawal, or if the study closes for any reason.

Conditions

Germ Cell Tumor; Seminoma; Non-seminomatous Germ Cell Tumor; Ovarian Germ Cell Tumor

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate

  determined by the proportion of complete responses, partial responses, and stable disease for at least 3 months of therapy using RECIST 1.1 while including markers AFP/ beta-hcg.

  Start of the treatment until time of death or last follow up visit (up to 2 years)

Secondary Outcomes (4)

• Objective response rate

  Start of the treatment until time of death or last follow up visit (up to 2 years)

• Overall survival

  Start of the treatment until time of death or last follow up visit (up to 2 years)

• Incidence of Adverse Events

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

• Progression free survival

  Start of the treatment until time of death or last follow up visit (up to 2 years)

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Patients will be treated with Cabozantinib 60mg orally daily continuously until disease progression, unacceptable toxicity, or trial closure.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Patients will be treated with Cabozantinib 60mg orally daily continuously until disease progression, unacceptable toxicity, or trial closure.

Cabozantinib

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Histological or serological evidence of germ cell tumor, including seminoma, non-seminoma, and women with ovarian GCTs.
• Must have progressed after first-line cisplatin based combination chemotherapy AND demonstrated progression following at least one salvage regimen for advanced germ cell and now considered incurable with standard therapies, including further chemotherapy or surgery.
• "Failure" of prior therapy is defined as: 5.1.1. 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 5.1.3. 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: Subjects 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) are eligible
• Subjects with late relapse (\>2 years from previous chemotherapy) not amenable to resection are eligible if they have received first line platinum based chemotherapy and are deemed not amenable to surgical resection (no need for 1 salvage regimen in late relapse patients to be eligible).
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate laboratory values obtained within 10 days prior to registration for protocol therapy and as defined below:
• Hemoglobin ≥9g/dL 10.2. WBC ≥2500/μL 10.3. Absolute neutrophil count ≥1500/mm3 10.4. Platelet count ≥100,000/mm3 10.5. Total bilirubin ≤1.5 X ULN except patients with documented Gilbert's syndrome (≤3 X ULN) 10.6. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤3 X ULN; for patients with hepatic metastases, ALT and AST ≤5 X ULN; ALP ≤5 X ULN with documented bone metastases.
• Serum albumin ≥ 2.8 g/dl 10.8. (PT)/INR or partial thromboplastin time (PTT) test \< 1.5x the laboratory ULN

You may not qualify if:

• Prior treatment with Cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Subjects who have not received ≥1 salvage treatment regimens (except late relapse) or have further potentially curative treatment options.
• Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks prior to first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic at the time of first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks, or any other radiation therapy within 4 weeks prior to first dose of study treatment.
• Expecting to father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Treatment with investigational agent, any type of cytotoxic, biologic or other systematic anticancer therapy within 28 days prior to registration for protocol therapy.
• Subjects with another active malignancy is not allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason \< Grade 7 prostate cancers, or other cancer for which the subject has not required therapy for ≥1 year.
• 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:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• 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.
• c.1 Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment.

Sponsors & Collaborators

• Jennifer King: lead
• Exelixis: collaborator
• JDS Foundation Testis Cancer Clinical Trials Support Fund: collaborator

Study Sites (1)

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal; Seminoma; Nonseminomatous germ cell tumor

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Germinoma

Study Officials

• Jennifer King, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 6, 2021
• Study Start: June 10, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

US (1)