Secured Access to Pembrolizumab for Patients With Selected Rare Cancer Types

NCT03012620 | Completed Phase 2 DMC

• 2 other identifiers: UC-0105/16122016-002260-14
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, non-randomised, open-label, multicentric study to investigate the efficacy and safety of pembrolizumab monotherapy in 7 cohorts of patients with specific rare cancers who have unresectable locally advanced or metastatic disease, which is resistant or refractory to standard therapy, or for which standard therapy does not exist, or is not considered appropriate, and for which no other experimental treatment options are available, in order to identify subsets of patients that may benefit from treatment

Conditions

Sarcoma; Ovarian Neoplasm; Central Nervous System Neoplasm; Thyroid Neoplasm; Carcinoma, Neuroendocrine; Neoplasms, Germ Cell and Embryonal; NK/T-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  ORR will be assessed per cohort by an IRC according to RECIST v1.1.

  measured at the first scheduled disease assessment following study treatment initiation (Day 84, ± 7 days)

Secondary Outcomes (9)

• Progression-free survival

  From date of inclusion until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months

• Overall survival

  From date of inclusion until the date of death from any cause, assessed up to 36 months

• Best response

  From inclusion up to 36 months

• Response duration

  from first observation of objective response until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months

• Time to response

  from inclusion first observation of objective response, assessed up to 36 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab 200 mg IV as a 30 minute infusion on Day 1 of every 21 day cycle

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Treatment

Also known as: MK-3475, KEYTRUDA

Pembrolizumab

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient information sheet and written informed consent form signed.
• Histologically confirmed diagnosis of a pathology corresponding to one of the following selected cancer types:
• Rare sarcoma: Alveolar soft part sarcoma, Chordoma, Dedifferentiated chondrosarcoma, epithelioid sarcoma, sarcoma with loss of INI1, malignant rhabdoid tumours, myxoid liposarcoma, angiosarcoma of the scalp, radiation induced sarcomas.From the 51st patient included in this cohort, only the following histological types will be selected: Alveolar soft part sarcoma, Chordoma, SMARCA4-malignant rhabdoid tumours and Desmoplastic small-round-cell tumor.
• Rare ovarian cancer: recurrent or relapsed; sex cord tumour, germ cell tumour (immature teratoma, non seminomatous germ cell \& dysgerminoma), low-grade serous carcinoma, mucinous carcinoma, clear cell adenocarcinoma, small cell carcinoma, and carcinosarcoma - with histological confirmation following review by members of the Tumeurs Malignes Rares Gynécologiques (TMRG) network (French rare gynaecological tumour group).From the 51st patient included in this cohort, only the following histological types will be selected: teratoma, low-grade serous carcinoma and ovarian small cell carcinoma hypercalcemic type (SCOOHT).
• Primary central nervous system lymphoma (PCNSL): refractory primary intraocular and CNS lymphoma.From the 51st patient included in this cohort, only CNS lymphoma will be selected.
• Rare thyroid cancer: differentiated thyroid carcinoma (Papillary, follicular, Hurthle cell (oncocytic), poorly differentiated thyroid carcinoma), medullary thyroid carcinoma, anaplastic thyroid carcinoma.
• Rare malignant neuroendocrine tumour: poorly differentiated tumours refractory after 2 lines of chemotherapy, well differentiated tumours refractory after 4 lines of treatment, carcinoid tumours after 2 lines of treatment.
• Germ-cell cancer progressing after standard therapy.
• Natural killer T-cell lymphoma: extranodal NK/T-cell lymphoma regardless of localization that is resistant or refractory to prior L-asparaginase therapy.
• Metastatic disease or unresectable locally advanced malignancy that is resistant or refractory to standard therapy or for which standard therapy does not exist or is not considered appropriate by the Investigator.
• Aged ≥18 years old for cohort 2 to 7 and aged ≥15 years old for patients included in cohort 1 (rare sarcoma).
• Measurable disease according to RECIST v1.1 guidelines for solid tumours; or International primary central nervous system lymphoma cooperative group (IPCG) response criteria for patients in the PCNSL cohort. For patients with germ-cell cancer measurable disease is defined as measurable according to RECIST v1.1 and / or abnormal levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH). For patients with NK/T-cell lymphoma measurable disease is defined as focal uptake in at least one nodal or extra-nodal site with a Lugano 5-PS score of 4 or 5.
• Able to provide a Formalin-fixed/paraffin-embedded (FFPE) biopsy sample of a metastatic site or primitive tumour tissue.
• Note: Patients for whom suitable archived biopsy material is not available must be willing to undergo a biopsy of a tumour lesion prior to study entry, unless this is medically contraindicated (e.g. site inaccessible or patient safety concerns).
• Patients must have a mandatory treatment-free interval of at least 21 days following previous systemic anti-cancer treatments.

You may not qualify if:

• Prior treatment with an anti-PD1 or anti-PD-L1 antibody
• Eligible, and willing, to participate in a clinical trial of an alternative anticancer therapy targeting their disease which is open to accrual in France.
• Concurrent steroid medication at a dose greater than prednisone 10 mg/day or equivalent. For patients with PCNSL or germ-cell cancer, concurrent steroid medication at a dose greater than prednisone 20 mg/day or equivalent.
• 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.
• History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• History of severe hypersensitivity reaction to any monoclonal antibody therapy
• Radiotherapy (except for brain and extremities) within 21 days prior to the first administration of IP.
• Treatment with other investigational drugs or participation in another clinical trial within 21 days prior to the first administration of IP or concomitantly with the trial.
• Has known symptomatic central nervous system (CNS) metastases. Patients 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.
• Has known carcinomatous meningitis or a history of leptomeningeal disease, except for patients with primary CNS lymphoma.
• Serum creatinine \>1.5 x ULN or glomerular filtration rate (GFR) \<50 ml/min.
• Other malignancies within the past 5 years other than basal cell skin cancer or in situ carcinoma of the cervix.
• Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy.
• Active or chronic hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies), or a known history of active Tuberculosis bacillus.
• Has received a live vaccine within 30 days of planned start of study treatment. Note: Seasonal influenza vaccines for injection are generally inactivated vaccines and are allowed.

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• Ligue contre le cancer, France: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Gustave Roussy Cancer Campus

Villejuif, France

Location

Related Publications (1)

• Blay JY, Chevret S, Le Cesne A, Brahmi M, Penel N, Cousin S, Bertucci F, Bompas E, Ryckewaert T, Soibinet P, Boudou-Rouquette P, Saada Bouzid E, Soulie P, Valentin T, Lotz JP, Tosi D, Neviere Z, Cancel M, Ray-Coquard I, Gambotti L, Legrand F, Lamrani-Ghaouti A, Simon C, Even C, Massard C. Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSe Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial. Lancet Oncol. 2023 Aug;24(8):892-902. doi: 10.1016/S1470-2045(23)00282-6. Epub 2023 Jul 7.

  PMID: 37429302 DERIVED

MeSH Terms

Conditions

Sarcoma; Ovarian Neoplasms; Central Nervous System Neoplasms; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Neoplasms, Germ Cell and Embryonal; Lymphoma, Extranodal NK-T-Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Nervous System Neoplasms; Nervous System Diseases; Head and Neck Neoplasms; Thyroid Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Study Officials

• Christophe Massard, MD

  Gustave Roussy Cancer Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2017
• First Posted: January 6, 2017
• Study Start: July 5, 2017
• Primary Completion: December 26, 2022
• Study Completion: December 14, 2023
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)