Pembrolizumab in Subjects With Incurable Platinum-Refractory Germ Cell Tumors

NCT02499952 | Terminated Phase 2 Results DMC

• 1 other identifier: HCRN GU14-206
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, multi-institutional, single arm phase II trial of pembrolizumab in patients with incurable platinum refractory germ cell tumors. No randomization or blinding is involved.

Conditions

Germ Cell Neoplasms; Testicular Neoplasms; Non Seminomatous Germ Cell Tumors; Mediastinal Neoplasms; Genital Neoplasms, Male; Genital Neoplasms, Female; Ovarian Neoplasms

Keywords

Pembrolizumab; MK-3475; PMNSGCT; PD-L1; Non Seminomatous Germ Cell Tumors

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  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.

  up to 18 weeks

Secondary Outcomes (3)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability Using Common Terminology Criteria for Adverse Events (CTCAE) V4.

  Every week while patient is receiving pembrolizumab, assessed for up to 52 weeks

• Disease Assessment for Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Criteria

  From the start of treatment D1 every 6 weeks for initial 18 weeks, assessed for up to 52 weeks

• Disease Assessment for Duration of Disease Response

  From the start of treatment D1 every 6 weeks for initial 18 weeks, assessed for up to 52 weeks

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Pembrolizumab

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or after 52 weeks of therapy.

Also known as: MK-3475

Experimental Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nasser Hanna, M.D.: lead
• Hoosier Cancer Research Network: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Adra N, Einhorn LH, Althouse SK, Ammakkanavar NR, Musapatika D, Albany C, Vaughn D, Hanna NH. Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206. Ann Oncol. 2018 Jan 1;29(1):209-214. doi: 10.1093/annonc/mdx680.

  PMID: 29045540 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Nonseminomatous germ cell tumor; Mediastinal Neoplasms; Genital Neoplasms, Male; Genital Neoplasms, Female; Ovarian Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Thoracic Neoplasms; Mediastinal Diseases; Thoracic Diseases; Respiratory Tract Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Ovarian Diseases; Adnexal Diseases

Limitations and Caveats

This study was terminated early due to not meeting the primary efficacy endpoint at a pre-planned interim analysis.

Results Point of Contact

• Title: Clinical Data Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Nasser Hanna, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

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: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 16, 2015
• Study Start: January 1, 2016
• Primary Completion: January 13, 2017
• Study Completion: January 13, 2017
• Last Updated: July 11, 2022
• Results First Posted: April 17, 2018

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)