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Ewing SarcomaPhase 2NCT04129151

Palbociclib + Ganitumab In Ewing Sarcoma

A Phase 2 study testing Palbociclib and Ganitumab in people with Ewing Sarcoma and Ewing's Sarcoma Recurrent, run by Dana-Farber Cancer Institute at 3 sites 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 research study is designed to study the combination of two drugs, palbociclib and ganitumab, as a potential treatment for Ewing sarcoma. The names of the study drugs involved in this study are: Palbociclib Ganitumab Read more about this study

Who is it for?
Ages 12 to 50 years
Conditions the study is for
Ewing Sarcoma, Ewing's Sarcoma Recurrent
What is being tested?
Palbociclib and Ganitumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesUnited States
Study dates
5 Dec 2019to 15 Dec 2022
Phase
Phase 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 to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age ≥ 12 years and ≤ 50 years at time of enrollment.
  • Karnofsky performance status ≥ 50% for patients ≥16 years of age and Lansky ≥ 50% for patients <16 years of age (see Appendix A)
  • Disease Requirement: Participants must have relapsed or refractory Ewing sarcoma with:
  • RECIST measurable disease at study entry, including at least one RECIST measurable site that has either not been previously radiated or that has had progression after prior radiotherapy;
  • Histologic diagnosis consistent with Ewing sarcoma or PNET; and
  • Molecular evidence of translocation involving EWSR1 or FUS (also known as TLS), such as FISH, RT-PCR, or next generation sequencing. If the translocation partner is known it must be of the ETS family (i.e. FLI1 or ERG).
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  • Participants must have disease for which standard curative or palliative measures do not exist or are no longer effective.
  • Patients must have fully recovered (Common Terminology Criteria for Adverse Events [CTCAE] version 5 Grade ≤1) from the acute toxic effects of all prior anti-cancer therapy except organ function as noted in Section 3.1.6. Patients must meet the following minimum washout periods prior to enrollment:
  • Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy (42 days for nitrosourea or mitomycin C).
  • Radiotherapy:
  • At least 14 days after local palliative XRT (small port);
  • At least 90 days must have elapsed after craniospinal XRT or if >50% radiation of pelvis;
  • At least 6-months must have elapsed following TBI or thoracic radiation involving the lungs;
  • At least 42 days must have elapsed if other substantial bone marrow radiation;
  • Small molecule biologic therapy: At least 7 days following the last dose of a biologic agent. For agents with known adverse events occurring beyond 7 days, this duration must be extended beyond the time in which adverse events are known to occur. If extended duration is required, this should be discussed and approved by the study chair.
  • Monoclonal antibody: At least 21 days must have elapsed after the last dose of antibody.
  • Myeloid growth factors: At least 14 days following the last dose of long-acting growth factor (e.g. Neulasta®) or 7 days following short-acting growth factor.
  • Immunotherapy: At least 4 weeks since the completion of immunotherapy (e.g. tumor vaccines) aside from monoclonal antibodies with immune effects covered under Section 3.1.5.4.
  • Stem Cell Infusion or Cellular Therapies: The patient must have no evidence of graft versus host disease and at least 42 days must have elapsed after transplant, stem cell infusion, or cellular therapy.
  • Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Biopsy and central line placement/removal are not considered major surgery.
  • CDK4/6 and IGF-1R inhibitors: The participant must not have received a prior CDK4/6 inhibitor. Prior therapy with IGF-1R inhibitor is allowed if the patient did not relapse while on IGF-1R therapy. Patients must not have received prior therapy with a combination of CDK4/6 inhibitor and IGF-1R inhibitor.
  • Participants must have normal organ function as defined below.
  • Hematologic Requirements for Subjects without Known Bone Marrow Involvement by Disease:
  • Absolute neutrophil count ≥ 1000 /uL
  • Hemoglobin ≥ 8 g/dL (transfusion allowed)
  • Platelets ≥100,000 /uL and transfusion independent, defined as not receiving a platelet transfusion for at least 7 days prior to CBC documenting eligibility.
  • Hematologic Requirements for Subjects with Bone Marrow Involvement by Disease as Demonstrated on Clinically-Indicated Bone Marrow Biopsy:
  • Absolute neutrophil count >750 /uL
  • Hemoglobin ≥ 8 g/dL (transfusion allowed)
  • Platelets ≥50,000 /uL and transfusion independent, defined as not receiving a platelet transfusion for at least 7 days prior to CBC documenting eligibility.
  • Not known to be refractory to platelet or red cell transfusions.
  • Hepatic Function:
  • Total bilirubin ≤ 1.5 x upper limit of normal for age Patients with Gilbert's syndrome with a total bilirubin < 2 x upper limit of normal for age and a direct bilirubin within normal limits are permitted.
  • ALT (SGPT) ≤ 135 U/L For the purpose of this study, the ULN for ALT is 45 U/L
  • AST (SGOT)≤ 90 U/L For the purpose of this study, the ULN for AST is 90 U/L
  • Serum albumin ≥ 2 g/dL
  • Renal Function:
  • -- A serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Male Female
  • 12 to < 13 years 1.2 1.2
  • 13 to < 16 years 1.5 1.4
  • ≥ 16 years 1.7 1.4 Or
  • Creatinine clearance ≥ 70 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Adequate Cardiac Function: QTc ≤ 480 msec on ECG
  • Adequate GI Function: Diarrhea < grade 2 by CTCAE version 5
  • Adequate Metabolic Function: Fasting glucose ≤ 160 mg/dL (or < 8.9 mmol/L) without the use of antihyperglycemic agents. If random glucose ≤ 160 mg/dL (or ≤ 8.9 mmol/L), fasting value does not need to be obtained.
  • Additional Agent-Specific Requirements
  • Patients must be able to swallow capsules.
  • For patients with CNS metastatic disease, any baseline neurologic deficits (including seizure) must be stable for at least one week prior to study enrollment.
  • Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, using an institutionally approved informed consent procedure.

Who cannot join

  • Patients must not be receiving any of the following concomitant medications:
  • -- Pharmacologic doses of systemic corticosteroids unless for CNS metastatic disease. For patients with CNS metastatic disease receiving corticosteroids, they should be on a stable or decreasing dose over the 7 days prior to registration Section 3.1.6.7 of protocol document. For all patients, receipt of systemic physiologic replacement steroids, topical and/or inhaled corticosteroids is acceptable.
  • Patients receiving medications that are strong inhibitors or inducers of CYP3A4 within 7 days of enrollment (refer to Appendix B, Table 10 for prohibited medications)
  • Patients receiving medications that cause significant QTc prolongation as outlined in Table 12 of Appendix B.
  • Patients who have had tumor molecular testing with sequencing of the RB1 gene and were found to have RB1 mutation or loss will be excluded.
  • Patients with a history of pneumonitis will be excluded.
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  • Pregnant participants will not be entered on this study given that the effects of palbociclib and ganitumab on the developing human fetus are unknown.
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with palbociclib and ganitumab, breastfeeding mothers are not eligible.
  • Participants of child-bearing or child-fathering potential must agree to use adequate contraception (hormonal birth control; intrauterine device; double barrier method; or total abstinence) throughout their participation, including up until 30 days after last dose of palbociclib or ganitumab, whichever was administered last.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or ganitumab.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Participants with a personal history of any of the following: syncope due to an intrinsic cardiac etiology (note that syncope due to vasovagal episodes or dehydration/orthostasis would NOT exclude a participant), pathologic ventricular arrhythmias (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
  • Patients with known HIV, hepatitis B, and/or hepatitis C (testing not required as part of screening).
  • Patients with a known history of type 1 or type 2 diabetes mellitus.
  • Patients with gastrointestinal disease or disorder that could interfere with absorption of palbociclib, such as bowel obstruction or inflammatory bowel disease.
  • Patients < 40 kg will be excluded given use of palbociclib at non-weight / non-BSA based flat dosing.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Phase 2 Trial of Palbociclib and Ganitumab in Patients With Relapsed or Refractory Ewing Sarcoma

This research study is designed to study the combination of two drugs, palbociclib and ganitumab, as a potential treatment for Ewing sarcoma.

The names of the study drugs involved in this study are:

  • Palbociclib
  • Ganitumab
Read the detailed description

This research study involves participants taking a medicine that inhibits proteins in cancer cells called CDK4 and CDK6 (palbociclib) in combination with a medicine that inhibits a protein called IGF-1R (ganitumab). This study is designed to see if these drugs are safe when given together and whether they are effective in treating Ewing sarcoma.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or drug combination to learn whether the drug(s) works in treating a specific disease. "Investigational" means that the drug or combination is being studied.

The U.S. Food and Drug Administration (FDA) has not approved ganitumab as a treatment for any disease.

The U.S. Food and Drug Administration (FDA) has not approved palbociclib for this specific disease but it has been approved for another cancer.

This research study is:

  • Testing whether palbociclib and ganitumab are safe when given together and effective in treating Ewing sarcoma.
  • Testing markers in the blood and in tumor tissue to see if there are certain features of the tumor that may indicate this combination of drugs is effective or not effective
Being tested
Palbociclib, Ganitumab
Keywords
Relapsed or refractory Ewing sarcoma, Solid Tumor, Childhood, Sarcoma, Ewing sarcoma
Medical subject headings
Sarcoma, Ewing, Recurrence, Sarcoma

What participants receive

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

  • PalbociclibDrug

    Also called Ibrance®

    Oral, per protocol pre determined dosage, once a day for 21 days

  • GanitumabDrug

    Also called AMG-479

    -Intravenous, per protocol predetermined dosage, twice per cycle

Study groups in NCT04129151
Study groupRoleWhat they receive
PALBOCICLIB and GANITUMABExperimentalParticipants receive up to 12 cycles of therapy (cycle duration=28 days). * Palbociclib: Oral, 100mg, daily on days 1-21 * Ganitumab: Intravenous, 18mg/kg, days 1, 15 Per protocol, participants were monitored for dose-limiting toxicity over cycle one according to an interim safety analysis. The safety monitoring rule was triggered after 3 patients had enrolled, prompting an amendment according to Contingency Plan A which was a reduction of the palbociclib dose from 125mg (days 1-21).
Receives: Drug: Palbociclib; Drug: Ganitumab

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    Measured: Participants were followed up to 10.8 months

  2. Grade 3/4 Treatment-Related Toxicity Rate

    The proportion of participants who experienced a maximum grade 3 or 4 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms

    Measured: Participants were followed up to 11.8 months.

Secondary outcomes (2)

  1. 6-month Progression Free Survival (PFS6)

    PFS6 is the percent probability estimate at 6 months based on the Kaplan-Meier method. PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

    Measured: Participants were followed up to 6 months.

  2. 6-month Overall Survival (OS6)

    OS6 is the percent probability estimate at 6 months based on the Kaplan-Meier method. Overall survival was defined as the time from study enrollment to death. Participants alive were censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

    Measured: Participants were followed up to 6 months.

Timeline

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

  1. First posted16 Oct 2019
  2. Study start5 Dec 2019
  3. Primary completion15 Dec 2022
  4. Study completion15 Dec 2022

Why it stopped: The study closed early due to discontinuation of ganitumab supply.

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
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04129151
Sponsor's protocol ID
19-373
Status last verified
Jul 2024
First submitted
14 Oct 2019
Last updated
1 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: contact Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • Shulman DS, Merriam P, Choy E, Guenther LM, Cavanaugh KL, Kao PC, Posner A, Bhushan K, Fairchild G, Barker E, Klega K, Stegmaier K, Crompton BD, London WB, DuBois SG. Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma. Cancer Med. 2023 Jul;12(14):15207-15216. doi: 10.1002/cam4.6208. Epub 2023 Jun 12.

    PubMed 37306107

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palbociclib and Ganitumab in people with Ewing Sarcoma and Ewing's Sarcoma Recurrent, run by Dana-Farber Cancer Institute at 3 sites 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 49 inclusion and 16 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 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

Yes. Results are posted in the registry (first posted 17 Jul 2024). 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?

Objective Response Rate (ORR) (time frame: Participants were followed up to 10.8 months). 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 NCT04129151, 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 1 Aug 2024.

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