Palbociclib + Ganitumab In Ewing Sarcoma

NCT04129151 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-373
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Ewing Sarcoma; Ewing's Sarcoma Recurrent

Keywords

Relapsed or refractory Ewing sarcoma; Solid Tumor, Childhood; Sarcoma; Ewing sarcoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Participants were followed up to 10.8 months

• 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

  Participants were followed up to 11.8 months.

Secondary Outcomes (2)

• 6-month Progression Free Survival (PFS6)

  Participants were followed up to 6 months.

• 6-month Overall Survival (OS6)

  Participants were followed up to 6 months.

Study Arms (1)

PALBOCICLIB and GANITUMAB

EXPERIMENTAL

Participants 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).

Drug: Palbociclib; Drug: Ganitumab

Interventions

Palbociclib DRUG

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

Also known as: Ibrance®

PALBOCICLIB and GANITUMAB

Ganitumab DRUG

-Intravenous, per protocol predetermined dosage, twice per cycle

Also known as: AMG-479

PALBOCICLIB and GANITUMAB

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• 1 Million 4 Anna Foundation: collaborator
• Carson Sarcoma Foundation: collaborator
• Teaming up to Fight Childhood Cancer: collaborator
• ChemoWarrior: the eli sidler foundation: collaborator
• i-ROK Foundation: collaborator
• Rutledge Cancer Foundation: collaborator
• Alan B. Slifka Foundation: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 37306107 RESULT

MeSH Terms

Conditions

Sarcoma, Ewing; Recurrence; Sarcoma

Interventions

palbociclib; ganitumab

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study terminated before full accrual.

Results Point of Contact

• Title: David S Shulman, MD
• Organization: Dana-Farber Cancer Institute

david_shulman@dfci.harvard.edu

617-632-6670

Study Officials

• David Shulman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 16, 2019
• Study Start: December 5, 2019
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: August 1, 2024
• Results First Posted: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)