Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors

NCT03158064 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-160
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety and effectiveness of durvalumab with tremelimumab in patients with relapsed or refractory germ cell tumors.

Conditions

Germ Cell Tumor; Nonseminomatous Germ Cell Tumor; Seminoma; Germinomatous Germ Cell Tumor; Dysgerminoma; Pineal Germ Cell Tumor

Keywords

17-160; durvalumab; tremelimumab; MEDI4736

Outcome Measures

Primary Outcomes (1)

• overall response rate (ORR)

  by RECIST v1.1

  1 year

Study Arms (1)

Duravalumab + Tremelimumab

EXPERIMENTAL

Duravalumab/Tremelimumab: Durvalumab and Tremelimumab will be administered by IV every 4 weeks for up to 4 doses/cycles, then Durvalumab by IV every 4 weeks starting at Week 16 for 9 doses (total treatment duration of 12 months). Participants enrolled now will receive tremelimumab \*300mg with durvalumab 1500mg for 1 cycle followed by 12 cycles of durvalumab 1500mg every 4 weeks or until lack of clinical benefit or unacceptable toxicity.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

1500 mg by IV

Also known as: MEDI4736

Duravalumab + Tremelimumab

Tremelimumab DRUG

75 mg by IV \*300mg

Duravalumab + Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at time of informed consent
• Body weight \> 30 kg
• Histologically confirmed diagnosis of GCT (nonseminoma or seminoma in men; non-dysgerminomas, dysgerminomas, or germinomas in women or patients with pineal gland GCT) at MSKCC of any primary site (includes female GCT and intracranial GCT).
• Evidence of measurable disease either by RECIST 1.1 or elevation of serum tumor markers (AFP \> 15 ng/mL or HCG \>2.2 mIU/ml).
• Patients must have progressed after at least one prior systemic therapy for GCT and meet one of the following criteria:
• a. Patients with evidence of progressive or recurrent GCT after progression prior high dose chemotherapy (HDCT) treatment, defined as meeting at least on of the following criteria: i. Tumor biopsy of new or growing or unresectable lesions demonstrating viable GCT. In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for this study.
• ii. Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
• iii. Development of new or enlarging lesions in the the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to rise.
• b. Patients deemed not to be a candidate for or benefit from potentially curative HDCT or other curative treatment options defined as follows: i. Patients with inadequate renal function for HDCT. ii. Patients who have had 3 or more lines of prior chemotherapy as this patient population has historically not benefitted from HDCT.
• iii. Patients with late relapse (relapse \> 2 years after last therapy) as this patient population has historically not benefitted from HDCT.
• iv. Patient with inadequate stem cell collection to move forward with HDCT. v. Patients with significant medical or psychosocial comorbidities that are felt to be a contraindication to HDCT by the treating investigator.
• NOTE: There is no maximum number of prior treatments allowed "Progression" after prior therapy is defined as any one of the following: NOTE: Patients with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery. In patients with rising tumor markers as their only evidence of disease progression where AFP is \<30 or HCG is \<15, alternate causes of increased levels of these markers should be ruled out. (e.g., hypogonadism by testosterone suppression of LH, hepatitis, use of marijuana).
• Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate normal organ and marrow function as defined below:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrolment in the present study
• Participation in another clinical study with an investigational product during the last 14 days
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 14 days prior to the first dose of study drug
• Major surgery within 28 days of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
• Radiation within 14 days of starting study treatment
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• A temporary period of steroids for different indications, at the discretion of the principal investigator (e.g., chronic obstructive pulmonary disease, radiation, nausea, etc)
• Any unresolved toxicity (\>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., alopecia, hearing loss, peripheral neuropathy).
• History of pulmonary fibrosis by imaging or biopsy (including secondary to bleomycin), pneumonitis (including drug induced) requiring steroids ≥ 3 weeks, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan with associated symptoms.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal; Nonseminomatous germ cell tumor; Seminoma; Dysgerminoma; Germinoma

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Study Officials

• Samuel Funt, MD

  Memorial Sloan Kettering Cancer Center

  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: May 16, 2017
• First Posted: May 17, 2017
• Study Start: May 15, 2017
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (7)