Brief Title
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma
Official Title
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma
Brief Summary
The proposed study will evaluate the safety and feasibility of neoadjuvant nivolumab +/-
ipilimumab in resectable MPM. In addition, maintenance nivolumab will be administered for 1
year following completion of standard bi-/tri-modality therapy.
Detailed Description
For Arm A 15 patients with resectable MPM will be enrolled and receive preoperative
nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to
planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and
Day +10).
Subsequent to full accrual to Arm A, 15 patients with resectable MPM will be enrolled and
receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each
timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for
scheduling surgery may take place between Day -3 and Day +10).
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Safety Profile of neoadjuvant nivolumab +/- ipilimumab in patients with resectable malignant pleural mesothelioma (MPM) with grade III/IV adverse events defined by CTCAE v5.0
Secondary Outcome
Pathological Response to neoadjuvant nivolumab +/- ipilimumab in resected tumor and lymph nodes in patients with resectable MPM defined as ≤10% residual viable tumor cells and pathologic complete response
Condition
Mesothelioma
Intervention
Nivolumab Injection
Study Arms / Comparison Groups
Arm A Nivolumab Only
Description: Receive preoperative nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
October 2, 2019
Completion Date
June 2026
Primary Completion Date
June 2025
Eligibility Criteria
Inclusion Criteria:
- Men and women ≥ 18 years old
- Primary tumor amenable to safe research biopsy. A tumor biopsy is required for study
entry.
- Histology proven epithelial or biphasic MPM
- Diagnostic core biopsy specimens must be reviewed by faculty pathologist at SKCC,
MDACC, or UMGCCC.
- Either a formalin fixed paraffin block that has been confirmed by a pathologist
to contain tumor or a minimum of twenty 5-micron tissue sections (slides) of
tumor biopsy sample must be available for biomarker evaluation (study pathologist
must review for adequacy of sampling). This can be obtained from archived tissues
if adequate, or from a new biopsy as needed.
- Stage I-III and deemed to be potentially surgically resectable as assessed by faculty
surgeon at SKCC, MDACC, or UMGCCC
- ECOG performance status 0-1
- Adequate organ function as follows:
- Leukocytes ≥ 2,000/mm3
- Absolute neutrophil count (ANC) ≥ 1000/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/Dl
- Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥40 mL/min (if using the
Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
- Total Bilirubin ≤ 1.5 x institutional ULN (except subjects with Gilbert Syndrome, who
can have total bilirubin < 3.0 mg/dL)
- AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 3 times the institutional upper limit
of normal
- Subjects must have adequate lung function to permit surgical resection determined by
pre-enrollment pulmonary function tests to include DLCO
- The effects of nivolumab on the developing human fetus are unknown. For this
reason, women of child-bearing potential (WOCBP) and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry and for the duration of study participation and for up to 23
weeks after the last dose of nivolumab. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately. Sexually active fertile men
must use effective barrier birth control if their partners are WOCBP for up to 31
weeks after the last dose of nivolumab. WOCBP must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within
two weeks of registration. Women must not be breastfeeding.
- Patient understands the study regimen, its requirements, risks and discomforts
and is able and willing to sign the informed consent form. Voluntary signed and
dated IRB/IEC approved written informed consent form in accordance with
regulatory and institutional guidelines must be obtained before the performance
of any protocol related procedures that are not part of normal patient care.
Subjects must be competent to report AEs, understand the drug dosing schedule and
use of medications to control AEs.
Exclusion Criteria:
- Stage I-III disease but deemed to be unresectable, a poor surgical candidate, or unfit
for study therapy as assessed by study investigators
- Pure sarcomatoid histology
- Subjects are excluded if they have an 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.
- Subjects are excluded if they 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. As there is potential for
hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a
predisposition to hepatotoxicity should be used with caution in patients treated with
nivolumab-containing regimen.
- Administration of chemotherapy or any other cancer therapy in the pre-operative
period.
- Subjects with active concurrent malignancies are excluded i.e. cancers other than MPM
(except non-melanoma skin cancers, cervical dysplasia, and in situ cancers of bladder,
stomach, breast, colon and cervix).
- Subjects with a history of symptomatic interstitial lung disease.
- Active systemic infection requiring therapy, as well as positive tests for hepatitis B
surface antigen or hepatitis C antibody.
- Known positive history or positive test for human immunodeficiency virus or Acquired
Immunodeficiency Syndrome (AIDS).
- History of allergy to study drug components.
- Women who are pregnant or nursing.
- Men with female partners (WOCBP) that are unwilling to use contraception
- Prior therapy with an anti-PD1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (or
any other antibody targeting T-cell co-regulatory pathways).
- History of any other condition that may require the initiation of anti-tumor necrosis
factor alpha (TNFα) therapies or other immunosuppressant medications during the study
- Underlying medical conditions that, in the Investigator's opinion, will make the
administration of study drug hazardous or obscure the interpretation of toxicity or
adverse events.
- Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for
treatment of either a psychiatric or physical (e.g. infectious disease) illness.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Patrick Forde, MD, 4109558893, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03918252
Organization ID
J1932
Secondary IDs
IRB00203283
Responsible Party
Sponsor
Study Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Bristol-Myers Squibb
Study Sponsor
Patrick Forde, MD, Principal Investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date
September 2020