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Carcinosarcoma of OvaryPhase 2NCT04149275

Cabozantinib Plus Nivolumab and Ipilimumab in Women With Recurrent Gynecologic Carcinosarcoma

A Phase 2 study testing Cabozantinib, Ipilimumab and Nivolumab in people with Carcinosarcoma of Ovary and Carcinosarcoma of Uterus, run by University of Alabama at Birmingham at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to test the safety of Cabozantinib in combination with Nivolumab and Ipilimumab and see what affects that this combination treatment has on those with recurrent carcinosarcomas. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Cabozantinib, Ipilimumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Feb 2021to Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed diagnosis of carcinosarcoma (independent of organ of origin).
  • Received at least one prior chemotherapy regimen for their cancer.
  • Must have measurable or evaluable lesion defined by iRECIST.
  • Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
  • Karnofsky performance status greater than or equal to 70% or ECOG PS = 0~2
  • Age ≥ 18 years.
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  • Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
  • White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
  • Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion.
  • Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases.
  • Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
  • Serum albumin ≥ 2.8 g/dl.
  • Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation: [(140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85
  • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol).
  • Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
  • Women of childbearing potential (WOCBP) ie. sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment.
  • Females should not breastfeed while receiving treatment on trial.
  • Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.

Who cannot join

  • 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.
  • Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 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 the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • 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. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
  • Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
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  • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
  • Low-dose low molecular weight heparins (LMWH) are permitted.
  • Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders: i. 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) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
  • Abdominal fistula, GI 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.
  • 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.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading or encasing any major blood vessels. f. Other clinically significant disorders that would preclude safe study participation.
  • Serious non-healing wound/ulcer/bone fracture. ii. Uncompensated/symptomatic hypothyroidism. iii. Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment [add reference for Fridericia formula].
  • Note: If a single ECG shows a QTcF with an absolute value > 500 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.
  • Inability to swallow tablets.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
  • Patients with concurrent cytotoxic chemotherapy or radiation therapy are excluded.
  • Patients with a serious chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment.
  • Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
  • Presence of a known active acute or chronic infection including: a urinary tract infection, HIV or viral hepatitis.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

Other trials in United States

About this study

Official title: A Phase II Single Arm Study of Cabozantinib Plus Nivolumab and Ipilimumab in Women With Recurrent Gynecologic Carcinosarcoma

The purpose of this study is to test the safety of Cabozantinib in combination with Nivolumab and Ipilimumab and see what affects that this combination treatment has on those with recurrent carcinosarcomas.

Read the detailed description

Primary Objectives:

  • To estimate the proportion of patients with recurrent carcinosarcoma, who survive progression-free for at least 6 months, treated with cabozantinib + nivolumab + ipilimumab in the second-line and beyond setting (per iRECIST).

Secondary Objectives:

  • To evaluate time to progression (Time Frame: From the date the patient received the first study treatment dose until the date of first documented progression, assessed up to 2 years). Progression Free Survival (PFS) according to iRECIST.
  • To determine the nature and degree of toxicity of cabozantinib + nivolumab + ipilimumab in this cohort of patients. Toxicity according to CTCAE v4.03
  • To estimate the overall survival (OS) of patients with carcinosarcoma treated with cabozantinib + nivolumab + ipilimumab

Exploratory Objectives:

  • To determine expression of biomarkers, which will include PD-L1 and MET expression by IHC, MSI status by NGS, and other relevant potential biomarkers.
  • To determine whether these marker expression levels alone or in combination are associated with response, PFS, and/or overall survival.
Keywords
Cabozantinib, Nivolumab, Ipilimumab, tyrosine-kinase inhibitor, anti-PD-1, anti-CTLA-4

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called tyrosine kinase inhibitor

    Treatment with oral Cabozantinib once daily

  • IpilimumabDrug

    Also called anti-CTLA-4

    IV administration of Ipilimumab on 21 day cycles

  • NivolumabDrug

    Also called anti-PD-1

    IV administration of Nivolumab on 21 day cycles, followed by Nivolumab maintenance on 28 day cycles

Study groups in NCT04149275
Study groupRoleWhat they receive
Cabozantinib + Nivolumab + IpilimumabExperimentalAll recurrent carcinosarcomas
Receives: Drug: Cabozantinib; Drug: Ipilimumab; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent progression free survival according to RECIST v1.1

    To estimate the proportion of patients with recurrent carcinosarcoma, who survive progression-free for at least 6 months, treated with cabozantinib + nivolumab + ipilimumab in the second-line and beyond setting (per iRECIST).

    Measured: Baseline through 6 months

Secondary outcomes (3)

  1. Percent time to progression according to RECIST v1.1

    To evaluate time to progression (Time Frame: From the date the patient received the first study treatment dose until the date of first documented progression, assessed up to 2 years). Progression Free Survival (PFS) according to iRECIST.

    Measured: Baseline through 2 years

  2. Percent overall survival according to RECIST v1.1

    To estimate the overall survival (OS) of patients with carcinosarcoma treated with cabozantinib + nivolumab + ipilimumab

    Measured: Baseline through 2 years

  3. Percent of patients with toxicity according to CTCAE v4.03

    To determine the nature and degree of toxicity of cabozantinib + nivolumab + ipilimumab in this cohort of patients. Toxicity according to CTCAE v4.03

    Measured: Baseline through 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2019
  2. Study startFeb 2021 (estimated)
  3. Primary completionFeb 2021 (estimated)
  4. Study completionFeb 2021 (estimated)

Why it stopped: Funding withdrawn by sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04149275
Sponsor's protocol ID
IRB-300003948
Status last verified
Feb 2021
First submitted
22 Oct 2019
Last updated
21 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: To Be Determined

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib, Ipilimumab and Nivolumab in people with Carcinosarcoma of Ovary and Carcinosarcoma of Uterus, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent progression free survival according to RECIST v1.1 (time frame: Baseline through 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04149275.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.

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