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Advanced MalignanciesPhase 1APPEASENCT03407976

Apatinib With Pembrolizumab in Previously Treated Advanced Malignancies

A Phase 1 study testing Apatinib and Pembrolizumab in people with Advanced Malignancies and Urothelial Carcinoma, run by University of Utah at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open label nonrandomized Phase I/ IIA trial designed to assess the safety, tolerability, and efficacy of apatinib in combination with pembrolizumab. Phase I will assess the safety of combining increasing oral daily doses of apatinib with a fixed dose of IV pembrolizumab every three weeks and will determine… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Apatinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
19 Jun 2018to 2 Jul 2020
Phase
Phase 1
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female subject aged ≥ 18 years.
  • One of the following advanced solid malignancies which qualifies for standard of care pembrolizumab treatment per FDA approval:
  • Locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant/adjuvant platinum-based therapy. Patients may have received any amount of platinum-based therapy.
  • Unresectable or metastatic MSI-H or dMMR solid tumors that have progressed during or following prior treatment and have no satisfactory alternative treatment options (including MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan).
  • Recurrent locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (as determined by an FDA-approved test) that have progressed on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.
  • Patients must have available and be willing to provide formalin fixed paraffin embedded tissue sample from archival tissue (patients who can't provide archival tissue will be offered an optional biopsy; lack of tissue will not be exclusionary).
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  • Have measurable disease based on RECIST 1.1. (For Phase 2 Subjects Only)
  • Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive, a serum pregnancy test will be required.
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for at least 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study drug.
  • ECOG Performance Status ≤ 1.
  • Adequate organ function as defined in the protocol
  • Recovery to baseline or Grade ≤ 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • Patients must be able to provide informed consent and be willing to sign an approved consent form that conforms to federal and institutional guidelines

Who cannot join

  • Previous treatment with and disease progression on a combination of a VEGF inhibitor and an immune checkpoint inhibitor. Patients who have been treated with and have progressed on a single agent VEGF inhibitor OR an immune checkpoint inhibitor will not be excluded.
  • Current use of immunosuppressive medication, EXCEPT for the following:
  • Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids.
  • Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone equivalent.
  • Steroids as premedication for hypersensitivity reactions.
  • Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent per treating physician's clinical judgment. Subjects with type 1 diabetes, vitiligo, psoriasis, hypothyroidism, or hyperthyroidism not requiring immunosuppressive medications are eligible.
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  • Prior organ transplant including allogenic hematopoietic stem cell transplant.
  • Active infection requiring intravenous antibiotics (must be completed prior to registration).
  • 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.
  • Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
  • Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
  • 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.
  • Any history of congenital long QT syndrome.
  • Presence of a non-healing wound.
  • Other clinically significant disorders that would preclude safe study participation including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, psychiatric conditions with active suicidal ideation within the past year; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to apatinib or pembrolizumab.
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
  • Known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or detectable HCV RNA if anti-HCV antibody screening test positive).
  • Live vaccine within 4 weeks of the first dose of pembrolizumab and while on trial is prohibited.
  • Packed red blood cell transfusions or erythropoietin therapy within 14 days prior to the study enrollment unless erythropoietin therapy has been used to maintain a stable condition for at least 1 month prior to the enrollment.
  • Palliative radiotherapy within 2 weeks of the first dose of study treatment.
  • Major surgery within 4 weeks of first dose of study medications. Minor procedures (e.g. port placement, endoscopy with intervention) within 2 weeks of first dose of study medications are allowed.
  • Chemotherapy, targeted small molecule therapy, or investigational therapy within 4 weeks of the first dose of study treatment.
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4 Grade ≥ 3).
  • Subjects taking prohibited medications as described in the protocol with the exception of systemic corticosteroids as defined in the protocol. A washout period of at least 5 elimination half-lives (or as clinically indicated) should occur for prohibited medications prior to the start of treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: A Phase I/II Open Label Study of the Safety and Efficacy of Apatinib Administered to Patients With Advanced Malignancies to Improve Sensitivity to Pembrolizumab in the Second- or Later-line Setting (APPEASE)

This is an open label nonrandomized Phase I/ IIA trial designed to assess the safety, tolerability, and efficacy of apatinib in combination with pembrolizumab. Phase I will assess the safety of combining increasing oral daily doses of apatinib with a fixed dose of IV pembrolizumab every three weeks and will determine the RP2D (Recommended Phase 2 Dose). Phase II will assess the efficacy of the RP2D of apatinib in combination with pembrolizumab and provide additional safety and tolerability data in three disease-specific cohorts

Being tested
Apatinib, Pembrolizumab
Medical subject headings
Carcinoma, Transitional Cell, Adenocarcinoma

What participants receive

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

  • ApatinibDrug

    Also called YN968D1

    Apatinib oral daily at starting dose 1, Dose Level 2 or Dose Level 3 in phase I, and then whichever is the maximum tolerated dosage will be used for all Phase II patients.

  • PembrolizumabDrug

    200 mg Q3 weeks IV

Study groups in NCT03407976
Study groupRoleWhat they receive
Apatinib and Pembrolizumab, all patientsExperimentalNot described
Receives: Drug: Apatinib; Drug: Pembrolizumab

What is being measured

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

  1. Incidence of dose limiting toxicities (DLTs) of Apatinib in combination with pembrolizumab

    Safety and tolerability of apatinib (rivoceranib) in combination with pembrolizumab in subjects with select advanced malignancies (urothelial carcinoma, MSI-H/dMMR solid tumors including colorectal cancer, and gastric or gastroesophageal junction GEJ adenocarcinoma) and determine the recommended Phase II dose (RP2D) for apatinib in combination with pembrolizumab. Adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs)

    Measured: 21 days, one cycle

  2. Objective Response Rate (ORR) (Phase II)

    Objective response rate (ORR) by RECIST 1.1

    Measured: 12 months

Secondary outcomes (2)

  1. Progression Free Survival (PFS)

    Measured: 5 years (Patients are expected to stay on treatment for approximately 12 months)

  2. Occurrence of Adverse Events and Serious Adverse Events

    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

    Measured: 12 months

Timeline

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

  1. First posted23 Jan 2018
  2. Study start19 Jun 2018
  3. Primary completion19 Aug 2019
  4. Study completion2 Jul 2020

Why it stopped: Funding source withdrew financial support prior to start of Phase II portion of study

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
open label nonrandomized Phase I/ IIA trial designed to assess the safety, tolerability, and efficacy of apatinib in combination with pembrolizumab
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03407976
Sponsor's protocol ID
HCI108884
Acronym
APPEASE
Status last verified
Jul 2020
First submitted
17 Jan 2018
Last updated
15 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gumbleton M, Allan S, Conway H, Boucher K, Marvin J, Hawks J, Burnett W, Van Brocklin M, Whisenant J, Gilcrease G, Gupta S. A phase I open-label study of the safety and efficacy of apatinib (rivoceranib) administered to patients with advanced malignancies to improve sensitivity to pembrolizumab in the second- or later-line setting (APPEASE). BMC Res Notes. 2023 Feb 16;16(1):16. doi: 10.1186/s13104-023-06283-5.

    PubMed 36797744

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Apatinib and Pembrolizumab in people with Advanced Malignancies and Urothelial Carcinoma, run by University of Utah 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 14 inclusion and 28 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: stopped early, as of the sponsor's last update on 15 Jul 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 stopped early (reason given: Funding source withdrew financial support prior to start of Phase II portion of study). Results are not available in the source record.

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?

Incidence of dose limiting toxicities (DLTs) of Apatinib in combination with pembrolizumab (time frame: 21 days, one cycle). The study lists 2 primary outcomes in all. 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 NCT03407976, which also lists 1 linked publication.

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 15 Jul 2020.

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