Pembrolizumab in Subjects With Incurable Platinum-Refractory Germ Cell Tumors
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|ClinicalTrials.gov Identifier: NCT02499952|
Recruitment Status : Terminated (Lack of Efficacy)
First Posted : July 16, 2015
Results First Posted : April 17, 2018
Last Update Posted : July 11, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Germ Cell Neoplasms Testicular Neoplasms Non Seminomatous Germ Cell Tumors Mediastinal Neoplasms Genital Neoplasms, Male Genital Neoplasms, Female Ovarian Neoplasms||Drug: Pembrolizumab||Phase 2|
OUTLINE: This is a multi-center study.
Eligible subjects must have received initial cisplatin-based combination therapy, such as bleomycin-etoposide-cisplatin (BEP), cisplatin-etoposide (EP), etoposide-ifosfamide-cisplatin (VIP), or similar regimens AND demonstrated progression following the administration of at least one 'salvage' regimen for advanced germ cell neoplasm, such as high dose chemotherapy, paclitaxel-ifosfamide-cisplatin (TIP), or vinblastine-ifosfamide-cisplatin (VeIP).
Pembrolizumab 200mg IV every 3 weeks until progression or toxicity. Treatment will continue for up to 52 weeks in the absence of prohibitive toxicities or disease progression.
The following screening labs to demonstrate adequate organ function must be performed within 10 days of treatment initiation:
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or hematopoietin (EPO) dependency (within 7 days of assessment)
- Serum creatinine ≤1.5 X upper limit of normal (ULN) OR
- Measured or calculated creatinine clearance ≥60 mL/min for subject with creatinine levels >1.5 X institutional ULN
- Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)
- Serum total bilirubin ≤ 1.5 X ULN OR
- Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
- Albumin >2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Single-Arm Multi-Center Trial Evaluating the Efficacy of Pembrolizumab in the Treatment of Subjects With Incurable Platinum-Refractory Germ Cell Tumors: Hoosier Cancer Research Network GU14-206|
|Actual Study Start Date :||January 2016|
|Actual Primary Completion Date :||January 13, 2017|
|Actual Study Completion Date :||January 13, 2017|
Experimental: Experimental Arm
200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or after 52 weeks of therapy.
Other Name: MK-3475
- Clinical Benefit Rate (CBR) [ Time Frame: up to 18 weeks ]
CBR of single agent pembrolizumab in subjects with refractory germ cell tumors (GCTs), determined by sum of complete responses, partial responses, and stable disease for at least 3 months using Immune Related Response Criteria (irRC).
Complete Response(irPR): Disappearance of all lesions in two consecutive observations not less than 4 wk apart.
Partial Response (irPR): decrease in tumor burden ≥50 %relative to baseline confirmed by a consecutive assessment at least 4 wk after first documentation.
Stable Disease (irSD): not meeting criteria for irCR or irPR, in absence of irPD.
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability Using Common Terminology Criteria for Adverse Events (CTCAE) V4. [ Time Frame: Every week while patient is receiving pembrolizumab, assessed for up to 52 weeks ]Toxicity and tolerability of pembrolizumab in subjects with refractory GCTs. All grade 3 and higher adverse events are reported.
- Disease Assessment for Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Criteria [ Time Frame: From the start of treatment D1 every 6 weeks for initial 18 weeks, assessed for up to 52 weeks ]ORR of single agent pembrolizumab in subjects with refractory GCTs, determined by sum of complete responses and partial responses for at least 3 months using RECIST 1.1 criteria
- Disease Assessment for Duration of Disease Response [ Time Frame: From the start of treatment D1 every 6 weeks for initial 18 weeks, assessed for up to 52 weeks ]Duration of disease response
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0 or 1 within 14 days prior to registration for protocol therapy.
- Subjects must have histological or serological proof of metastatic germ cell neoplasm (gonadal or extragonadal primary) with disease not amenable to cure with either surgery or chemotherapy. Subjects with seminoma and non-seminoma are eligible, as are women with ovarian GCTs.
- Subjects must have evidence of recurrent or metastatic carcinoma by one or more of the following: the appearance of metastatic disease on chest x-ray or CT scan, or the appearance of rising tumor marker: AFP or beta-HCG. NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed. Subjects with only evidence of disease as rising tumor marker AFP and beta-HCG will be provided alternate causes of increased serum levels of these markers are not present, such as cross reaction with luteinizing hormone (LH) (that can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana, or second primary tumor, etc.
- Subjects must have received initial cisplatin based combination therapy, such as bleomycin-etoposide-cisplatin (BEP), cisplatin-etoposide (EP), etoposide-ifosfamide-cisplatin (VIP), or similar regimens AND demonstrated progression following the administration of at least one 'salvage' regimen for advanced germ cell neoplasm, such as high dose chemotherapy, paclitaxel-ifosfamide-cisplatin (TIP), or vinblastine-ifosfamide-cisplatin (VeIP).
- "Failure" of prior therapy is defined as: a >25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy which are not amenable to surgical resection; the presence of new tumors which are not amenable to surgical resection; an increase in AFP or beta-hCG (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of failure). NOTE: Subjects with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery.
- Subjects are eligible after first line platinum based chemotherapy if their disease has relapsed and they have Primary Mediastinal Non Seminomatous Germ Cell tumor (PMNSGCT) or late relapse (> 2 years) not amenable to surgical resection.
- Subjects must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g., inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor investigator
- Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication . Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Measurable disease according to RECIST v1.1 obtained by imaging within 28 days prior to registration.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events (AE) due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. NOTE 1: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. NOTE 2: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e,. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Presence of interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with PD-1, PD-L1, or CTLA-4 inhibitors.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02499952
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||Nasser Hanna, M.D.||Hoosier Cancer Research Network|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Nasser Hanna, M.D., Sponsor-Investigator, Hoosier Cancer Research Network|
|Other Study ID Numbers:||
|First Posted:||July 16, 2015 Key Record Dates|
|Results First Posted:||April 17, 2018|
|Last Update Posted:||July 11, 2022|
|Last Verified:||July 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
Non Seminomatous Germ Cell Tumors
Neoplasms, Germ Cell and Embryonal
Genital Neoplasms, Male
Genital Neoplasms, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Endocrine System Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Immunological