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Ewing SarcomaPhase 1/2NCT03190174

Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers

A Phase 1/2 study testing Nab-Rapamycin and Nivolumab in people with Ewing Sarcoma and PEComa, run by Sarcoma Oncology Research Center, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study investigates the safety/toxicity and potential anti-tumor activity of sequential administration of nivolumab and escalating doses of the mammalian target of rapamycin (mTOR) inhibitor nab-rapamycin (ABI-009) in advanced Ewing's sarcoma, perivascular epithelioid cell tumor (PEComa), epithelioid sarcoma… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Ewing Sarcoma, PEComa, Epithelioid Sarcoma
What is being tested?
Nab-Rapamycin and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
24 Aug 2017to 2 Dec 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • A patient will be eligible for inclusion in this study only if all of the following criteria are met:
  • Patients must have a histologically confirmed diagnosis of Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors, that is either metastatic or locally advanced and for which surgery is not a recommended option.
  • Patients must have one or more measurable target lesions by CT scan or MRI. Measurable disease by RECIST v1.1.
  • Patients must not have been previously treated with a PD-1 inhibitor in combination with an mTOR inhibitor.
  • Prior treatment (investigational or other), chemotherapy, radiotherapy, surgery, or other therapeutic agents (except immunotherapy and mTOR inhibitors) is allowed, if completed after 5 half-lives or ≥28 days prior to enrollment, whichever is shorter.
  • Eligible patients, 12 years or older, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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  • Patients must have the following blood chemistry levels at screening (obtained ≤14 days prior to enrollment (local laboratory):
  • total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dl
  • Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases)
  • serum creatinine ≤1.5 x ULN
  • Adequate biological parameters as demonstrated by the following blood counts at screening (obtained ≤14 days prior to enrollment, local laboratory):
  • Absolute neutrophil count (ANC) ≥1.5 × 109/L;
  • Platelet count ≥100,000/mm3 (100 × 109/L);
  • Hemoglobin ≥9 g/dL.
  • Serum triglyceride <300 mg/dL; serum cholesterol < 350 mg/dL.
  • Male or non-pregnant and non-breast feeding female:
  • Females of child-bearing potential must agree to use effective contraception without interruption from 28 days prior to starting investigational product (IP) and while on study medication and have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation.
  • Male patients must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study. A second form of birth control is required even if he has undergone a successful vasectomy.
  • Life expectancy of >3 months, as determined by the investigator.
  • Ability to understand and sign informed consent.
  • Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.

Who cannot join

  • A patient will not be eligible for inclusion in this study if any of the following criteria apply:
  • Concurrent or prior immunotherapy with a PD-1 inhibitor in combination with an mTOR inhibitor.
  • Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A patient with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases ≥28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
  • Active gastrointestinal bleeding.
  • Pre-existing thyroid abnormality is allowed provided thyroid function can be controlled with medication.
  • Uncontrolled serious medical or psychiatric illness. Patients with a "currently active" second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pT2 with Gleason Score ≤ 6 and postoperative prostate-specific antigen (PSA) <0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥1 year).
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  • Liver-directed therapy within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cryotherapy/ablation) is allowed if these therapies did not affect the areas of measurable disease being used for this protocol.
  • Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection).
  • Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.
  • Unstable coronary artery disease or myocardial infarction during preceding 6 months.
  • Receiving any concomitant antitumor therapy.
  • Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
  • Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to receiving the first dose of ABI-009.
  • Known Human Immunodeficiency Virus (HIV).
  • Active Hepatitis B or Hepatitis C.
  • Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment
  • Autoimmune disease including rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis and motor neuropathy considered to be of autoimmune origin (e.g. Guillain-Barre Syndrome)
  • Systemic immunosuppression, including HIV positive status with or without AIDS
  • Skin rash (psoriasis, eczema) affecting > 25% body surface area
  • Inflammatory bowel disease (Crohn's or ulcerative colitis)
  • Ongoing or uncontrolled diarrhea within 4 weeks of trial enrollment
  • Recent history of acute diverticulitis, intraabdominal abscess or gastrointestinal obstruction within 6 months of trial enrollment, which are known risk factors for bowel perforation
  • Current, active or previous history of heavy alcohol abuse
  • Pituitary endocrinopathy
  • Adrenal insufficiency or excess

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

Other trials in United States

About this study

Official title: A Phase 1/2 Study Using Nivolumab and ABI-009 for Advanced Sarcoma, Advanced Carcinoma Treated With PD1 Inhibitors, and Tumors With Genetic Mutations Sensitive to mTOR Inhibitors

This study investigates the safety/toxicity and potential anti-tumor activity of sequential administration of nivolumab and escalating doses of the mammalian target of rapamycin (mTOR) inhibitor nab-rapamycin (ABI-009) in advanced Ewing's sarcoma, perivascular epithelioid cell tumor (PEComa), epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, high microsatellite instability (MSI-H)/ mismatch repair deficient (dMMR) metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors.

Read the detailed description

The primary objective of this study is to investigate the maximum tolerated dose (MTD) of ABI-009, an mTOR inhibitor, when given sequentially with nivolumab in advanced Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors.

The secondary objectives are to investigate the disease control rate (DCR) and progression free survival (PFS) using nivolumab/ABI-009 combination therapy in advanced Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors.

The exploratory objectives are (1) To correlate progression free survival (PFS) based on Immune-related Response Criteria (irRECIST) with that based on RECIST v1.1, and (2) To correlate PFS with programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in patients' tumors.

Being tested
Nab-Rapamycin, Nivolumab
Medical subject headings
Sarcoma, Ewing, Perivascular Epithelioid Cell Neoplasms, Sarcoma, Desmoid Tumors, Chordoma, Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell, Melanoma

What participants receive

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

  • Nab-RapamycinDrug

    Also called ABI-009

    Escalating doses of ABI-009 will be given IV over 30 min for 2 of every 3 weeks beginning Day 8 Cycle 2. Only nivolumab will be given in Cycle 1. At Dose Level 1, 3-6 patients will receive 56 mg/m^2; at Dose Level 2, 3-6 six patients will receive 75 mg/m^2; and at Dose Level 3, 3-6 patients will receive 100 mg/m^2.

  • NivolumabBiological

    Also called Opdivo

    A defined dose of nivolumab, 3 mg/kg, will be given IV over 30 minutes q 3 weeks

Study groups in NCT03190174
Study groupRoleWhat they receive
Arm 1ExperimentalThis is an open label, dose-seeking phase 1b study using a defined dose of nivolumab and escalating doses of Nab-Rapamycin (ABI-009) given intravenously. I. Dose Escalation Phase 1 Part of Study: The study will employ the standard "cohort of three" design. No intra-patient dose escalation will take place. II. Expansion Phase 1b Part of Study: Following dose escalation, an additional 22-28 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment up to 18 three-week cycles or until significant disease progression or unacceptable toxicity occurs.
Receives: Drug: Nab-Rapamycin; Biological: Nivolumab

What is being measured

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

  1. Maximum Tolerated Dose of ABI-009

    The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced dose-limiting toxicity (DLT), with the next higher dose level having at least two patients who experienced DLT.

    Measured: Week 6

Secondary outcomes (3)

  1. Disease Control Rate

    The disease control rate is the percent of patients with complete response, partial response and stable disease.

    Measured: 12 weeks

  2. Progression Free Survival

    Progression free survival is the time from start of treatment to disease progression or death.

    Measured: 24 weeks

  3. Overall Survival

    The overall survival is the time from treatment initiation to death.

    Measured: 30 weeks

Timeline

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

  1. First posted16 Jun 2017
  2. Study start24 Aug 2017
  3. Primary completion1 Dec 2021
  4. Study completion2 Dec 2021

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03190174
Sponsor's protocol ID
SOC-1701
Status last verified
Feb 2025
First submitted
2 Feb 2017
Last updated
17 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gonzalez-Angulo AM, Meric-Bernstam F, Chawla S, Falchook G, Hong D, Akcakanat A, Chen H, Naing A, Fu S, Wheler J, Moulder S, Helgason T, Li S, Elias I, Desai N, Kurzrock R. Weekly nab-Rapamycin in patients with advanced nonhematologic malignancies: final results of a phase I trial. Clin Cancer Res. 2013 Oct 1;19(19):5474-84. doi: 10.1158/1078-0432.CCR-12-3110.

    PubMed 24089446

  • Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nab-Rapamycin and Nivolumab in people with Ewing Sarcoma and PEComa, run by Sarcoma Oncology Research Center, LLC 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 21 inclusion and 25 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: finished, as of the sponsor's last update on 17 Feb 2025. 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 combined 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.

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?

Yes. Results are posted in the registry (first posted 17 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dose of ABI-009 (time frame: Week 6). 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 NCT03190174, which also lists 2 linked publications.

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 17 Feb 2025.

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