Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors

NCT03726281 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HBA_001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the clinical activity of nivolumab monotherapy, as measured by the investigator-assessed clinical benefit rate (CBR), in patients with platinum-recurrent or platinum-refractory metastatic germ cell tumors (GCT). CBR is defined by sum of complete responses (CR), partial responses (PR) and stable disease (SD) for at least 3 months, with stable or declining tumor markers (αFP and HCG), using Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

Conditions

Germ Cell Tumors

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR, %)

  number of patients with confirmed responses of a. complete responses (CR), disappearance of all imagiologic evidence of disease AND normalization of GCT tumor markers (αFP and HCG), or b. partial responses (PR) and stable diseases (SD) for at least 3 months, with stable, declining or normalized GCT tumor markers (αFP and HCG), divided by the total number of evaluable patients. Tumor response status will be assessed using RECIST 1.1.

  3 months

Secondary Outcomes (6)

• CR + marker-negative PR (%)

  3 months

• CR + PR with stable or declining tumor markers (αFP and HCG)

  3 months

• Time to response

  6 months

• Duration of clinical response

  24 months

• Progression Free Survival (PFS)

  24 months

Study Arms (1)

single-arm trial of Nivolumab

EXPERIMENTAL

Multi-institutional, single arm phase II trial with Simon's optimal two-stage design, to evaluate the clinical benefit of Nivolumab monotherapy in patients with platinum-recurrent or platinum-refractory metastatic GCT. No randomization or blinding is involved.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab 240 mg, IV

single-arm trial of Nivolumab

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent
• Male or female, aged 18 years
• Metastatic GCT, seminoma or non-seminoma, previously treated with standard doublet or triplet cisplatin-containing chemotherapy for metastatic disease in: a) second or further relapse from primary testicular, retroperitoneal or ovarian GCT; b) first or further relapse of PMNSGCT; c) primary-refractory GCT (defined as progression within 8 weeks of finishing first-line chemotherapy for advanced GCT); or d) "late relapse" (\> 2 years after cisplatinum-containing chemotherapy for metastatic GCT) that is not amenable to surgical resection.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
• Evidence of recurrent disease by imaging (CT or MR) or rising tumor markers (αFP or 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 and alternative causes of increased serum levels of these markers must be excluded (cross reaction with luteinizing hormone (LH) (that can be tested if needed by testosterone suppression of LH), liver disease, use of marijuana, or second primary tumor)
• Received initial cisplatin based combination therapy, such as BEP, EP, VIP, or similar regimens AND, for primary testicular or ovarian GCT, progression after at least one 'salvage' chemotherapy regimen (such as, TIP, VeIP, VIP or high dose chemotherapy with ASCT).
• "Failure" of prior therapy is defined as: a \>20% increase in the sum of the longest diameter of target lesions during prior therapy which is not amenable to surgical resection; the presence of new tumor lesions that are not amenable to surgical resection; an increase in αFP or HCG (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of treatment failure) in patients with metastatic disease. NOTE: Patients with clinically growing "teratoma" (normal or declining tumor markers and radiographic progression) should be considered for surgery.
• Use an adequate method of contraception starting with the first dose of study therapy through 5 months after the last dose of study therapy.
• Measurable disease according to RECIST v1.1 obtained by imaging within 28 days prior to registration.
• Non-measurable but evaluable disease associated increasing tumor markers (αFP and HCG) may be eligible, upon review by two PIs.

You may not qualify if:

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• History of allergy or hypersensitivity to study drug components.
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results.
• Patients with an active, known or suspected autoimmune disease.
• Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Diagnosis of immunodeficiency or current treatment with systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Known history of active Tuberculosis, Human Immunodeficiency Virus (HIV) or active Hepatitis B (i.e. HBsAg reactive) or Hepatitis C (i.e. HCV RNA \[qualitative\] is detected).
• Treatment with 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 (i.e. Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Treatment with chemotherapy, targeted small molecule therapy or radiation therapy within 3 weeks prior to study Day 1 or without recovery (ie. ≤ Grade 1) from AEs from such previously administered agents. Patients with alopecia and ≤ Grade 2 neuropathy are an exception to this criterion and qualify for the study.
• Patients with recent major surgery in the previous 14 days prior to starting therapy must have recovered adequately from the toxicity and/or complications from the intervention.
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis, other than previously treated brain metastases who are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment) and must be either off corticosteroids or on a stable or decrease dose ≤10 mg daily prednisone (or equivalent).
• Presence of interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Hospital Beatriz Ângelo: lead
• Universidade Nova de Lisboa: collaborator
• Bristol-Myers Squibb: collaborator
• Instituto de Patologia e Imunologia Molecular da Universidade do Porto: collaborator

Study Sites (1)

Hospital Beatriz Ângelo

Loures, 2674-514, Portugal

Location

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

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

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: October 11, 2018
• First Posted: October 31, 2018
• Study Start: October 1, 2018
• Primary Completion: June 30, 2019
• Study Completion: June 30, 2019
• Last Updated: August 21, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be available for the intire study, 4 years
• Access Criteria: Only health professionals from Hospital Beatriz Ângelo, that make parte of the trial team will have acess

Locations

PT (1)