Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types

NCT03012581 | Completed Phase 2 DMC

• 2 other identifiers: UC-0105/16112016-002257-37
• Study Type: interventional
• Target: 269
• 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 nivolumab monotherapy in 6 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.

Conditions

Carcinoma, Renal Cell; Head and Neck Neoplasm; Skin Neoplasms; Microsatellite Instability; Penile Neoplasms; Cancer With POLE Exonucleasic Domain Mutation

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)

Nivolumab

EXPERIMENTAL

Nivolumab 240 mg IV over 60 minutes every 14 days.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Treatment

Also known as: Opdivo

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: 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:
• Non-clear cell renal-cell carcinomas: papillary renal cell carcinoma (pRCC, type I, type II and non-classified pRCC), chromophobe RCC (ChRCC), renal medullary carcinoma (RMC), collecting duct/Bellini duct carcinoma (CDC), microphthalmia-associated transcription (MiT) family translocation renal cell carcinoma (tRCC), renal cell carcinoma with a prominent sarcomatoid component (sarcRCC).From the 51st patient included in this cohort, only the following histological type will be selected: collecting duct/Bellini duct carcinoma (CDC).
• Rare head and neck cancers: principal and accessory salivary gland tumours, facial tissue tumours.
• Rare skin cancers: adnexal carcinomas, basal cell carcinoma resistant to vismodegib.From the 51st patient included in this cohort, only the following histological type will be selected: Basal Cell carcinoma.
• Non-colorectal cancers with microsatellite instability determined locally by immunohistochemistry or polymerase chain-reaction (PCR)
• Squamous cell carcinoma of penis.
• Any non MSI-high cancer with POLE exonucleasic domain mutation (somatic or germline) in hotspots (codons 286, 411, 424 and 459) or other germline or somatic variants with high probability of pathogenesis according to in silico assessment by the INCa ad hoc biology group.
• 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.
• Measurable disease according to RECIST v1.1 guidelines for solid tumours.
• 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.
• Patients who have received previous systemic anticancer treatment and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 (according to NCI-CTCAE criteria, v 4.0) with the exception of Grade 2 alopecia.

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.
• 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.
• 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 carcinoma in situ 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
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Gustave Roussy Cancer Campus

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Head and Neck Neoplasms; Skin Neoplasms; Microsatellite Instability; Penile Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Penile Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Aurélien Marabelle, 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: June 16, 2017
• Primary Completion: December 22, 2022
• Study Completion: November 11, 2023
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)