A Phase II of Nivolumab Plus Ipilimumab in Non-resectable Sarcoma and Endometrial Carcinoma

NCT02982486 | Unknown Phase 2

• 1 other identifier: 0239/16
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine whether nivolumab plus ipilimumab are effective and safe in the treatment of sarcoma and endometrial carcinoma patients with somatic deficient MMR as a selection tool.

Conditions

Soft Tissue Sarcoma; Bone Sarcoma; Chondrosarcoma; Gastrointestinal Stromal Sarcoma; Ewing's Tumor Metastatic; Ewing's Tumor Recurrent; Osteosarcoma; Desmoplastic Small Round Cell Tumor

Keywords

nivolumab; ipilimumab; immunotherapy; PD-1 inhibitor; sarcoma

Outcome Measures

Primary Outcomes (1)

• Response to therapy as evaluated by RECIST 1.1

  complete and partial response

  36 months

Secondary Outcomes (4)

• Median Progression-free survival (PFS)

  36 months

• Progression-free survival (PFS) assessed at 12 weeks

  12 weeks

• Progression-free survival (PFS) assessed at 24 weeks

  24 weeks

• overall survival

  36 months

Study Arms (1)

Nivolumab and ipilimumab

EXPERIMENTAL

Nivolumab 240 mg IV every 2 weeks plus Ipilimumab 1 mg/m2 IV every 6 weeks

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

Ipilimumab 1 mg/kg every 6 weeks

Also known as: anti CTLA4

Nivolumab and ipilimumab

Nivolumab DRUG

Ninolumab 240 mg IV every 2 weeks

Also known as: Anti PD-1

Nivolumab and ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will sign the informed consent form before the initiation of any study procedure.
• Males and Females, 18 years or older
• Patients must have a FFPE tumor block, one representative hematoxylin and eosin (H\&E) and 20 unstained sarcoma/endometrial carcinoma tissue slides available for submission to pathology review; this step is mandatory prior to registration to confirm eligibility.
• Tumors must immune-stain negatively to one or more of the following proteins: MLH1, MSH2, MSH6 and PMS2
• Patients must have histologically confirmed bone or soft tissue sarcoma by pathology review or a diagnosis of FIGO grade 3 endometrioid cancer, serous, clear cell, or mixed high grade endometrial cancer.
• Measurable disease of sarcoma or endometrial carcinoma defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with CT scan or MRI, as \>20 mm by chest x-ray, or \>10 mm with calipers by clinical exam by RECIST 1.1.
• Locally advanced non-operable or metastatic disease
• \>= 1 prior systemic therapy for sarcoma or endometrial carcinoma, including adjuvant systemic therapy
• No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy =\< 21 days before study registration
• Eastern Cooperative Oncology Group ECOG performance status 0 or 1
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to first drug dose
• WBC ≥ 2000/μL
• Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x103/μL
• Hemoglobin \> 9.0 g/dL

You may not qualify if:

• Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Have a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• FIGO grade 1 or 2 endometrioid cancer.
• Have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of nivolumab/ipilimumab or has not recovered (i.e., to ≤ grade 1 or baseline) from adverse events due to a previously administered agent. Note, subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note, if a subject received major surgery, she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• No known or suspected allergy to nivolumab or study drug components and no history of severe hypersensitivity reaction to any monoclonal antibody
• Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
• As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
• Have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Known active pulmonary disease with hypoxia defined as:
• Oxygen saturation \< 85% on room air or Oxygen saturation \< 88% despite supplemental oxygen
• Pregnant and nursing women
• Eastern Cooperative Oncology Group (ECOG) performance status 3-4
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

Sponsors & Collaborators

• Assaf-Harofeh Medical Center: lead

Related Publications (1)

• Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.

  PMID: 26028255 BACKGROUND

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms; Chondrosarcoma; Gastrointestinal Stromal Tumors; Osteosarcoma; Desmoplastic Small Round Cell Tumor

Interventions

Ipilimumab; Nivolumab; spartalizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daniela Katz, M.D

  Assaf-Harofeh Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniela Katz, MD

CONTACT

97289778144; katzd@asaf.health.gov.il

Sharona Ben Ami

CONTACT

97289778003; sharonab@asaf.health.gov.il

Study Design

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

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 5, 2016
• Study Start: December 1, 2017
• Primary Completion: June 1, 2020
• Study Completion: December 1, 2020
• Last Updated: November 1, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share