Tremelimumab and Durvalumab With or Without Radiation Therapy in Patients With Relapsed Small Cell Lung Cancer

NCT02701400 | Completed Phase 2 Results DMC

• 4 other identifiers: IRB00086004NCI-2016-00026ESR-14-10531Winship3112-15
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized clinical trial studies how well tremelimumab and durvalumab with or without radiation therapy works in treating patients with small cell lung cancer that has returned after a period of improvement. Monoclonal antibodies, such as tremelimumab and durvalumab, may limit the ability of tumor cells to grow and spread by enhancing immune function. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving tremelimumab and durvalumab together with radiation therapy may lead to improved clinical benefit.

Conditions

Recurrent Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  Time from initiation of therapy to objective disease progress or death

  From initiation of systemic therapy to first documented disease progression, assessed through study completion, up to 2 years

• Objective Response Rate

  Disease response to therapy measured according to RECIST 1.1 criteria

  After every 2 cycles of treatment (1 cycle = 4 weeks), assessed through study completion, up to 2 years

Secondary Outcomes (2)

• Immune-related Objective Response Rate

  Assessed after every 2 cycles (1 cycle = 4 weeks) on treatment; assessed through study completion, up to 2 years

• Overall Survival

  From randomization until death from any cause, assessed through study completion, up to 2 years

Other Outcomes (1)

• Change From Baseline in the Proportion of Lymphocyte Subset (CD8+ICOS+) Between Baseline and On-Treament (End of Cycle 1)

  Result presented for assessment at baseline and the end of cycle 1.

Study Arms (2)

Arm I (tremelimumab, durvalumab)

EXPERIMENTAL

Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation.

Biological: Durvalumab; Biological: Tremelimumab

Arm II (RT, tremelimumab, durvalumab)

ACTIVE COMPARATOR

Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I.

Biological: Durvalumab; Radiation: Hypofractionated Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Biological: Tremelimumab

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: MEDI4736

Arm I (tremelimumab, durvalumab); Arm II (RT, tremelimumab, durvalumab)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated radiation therapy

Also known as: Hypofractionated Radiotherapy, Hypofractionation

Arm II (RT, tremelimumab, durvalumab)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SBRT

Arm II (RT, tremelimumab, durvalumab)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675,206, Ticilimumab

Arm I (tremelimumab, durvalumab); Arm II (RT, tremelimumab, durvalumab)

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 any locally-required authorization (e.g.,) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L (≥ 1500 per mm³)
• Platelet count ≥ 100 x 10⁹/L (≥ 100,000 per mm³)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5 x ULN
• Serum creatinine clearance (CL) \> 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
• Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥ 60 years old and no menses for ≥ 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy upon study entry
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

You may not qualify if:

• Patients must have histologically or cytologically confirmed small cell lung cancer
• Patients must have measurable disease, defined as at least one lesion (excluding the lesion for XRT) that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \> 20 mm with conventional techniques or as \> 10 mm with spiral computed tomography (CT) scan
• Patient must have failed or found to be intolerant of standard frontline platinum-based regimens and must not have received \> 2 prior lines of therapy (nota bene \[NB\]: retreatment with a platinum-based doublet for sensitive relapse counts as another line therapy; however substitution of cisplatin with carboplatin or vice versa due to toxicity does not count as a separate regimen)
• Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
• Ability to understand and the willingness to sign a written informed consent document
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrollment or randomization in the present study
• Treatment with an investigational product during the last 2 weeks
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), 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 (≤ 7 days or four half-lives, whichever is longer, prior to the first dose of study drug for subjects who have received prior tyrosine kinase inhibitors \[TKIs\] \[e.g., erlotinib, gefitinib and crizotinib\] and within 6 weeks for nitrosourea or mitomycin C)
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Any unresolved toxicity (\> Common Terminology Criteria for Adverse Events \[CTCAE\] 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., hearing loss, peripherally neuropathy)
• Any prior grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> grade 1
• Active or prior documented autoimmune disease within the past 2 years; NOTE: subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded

Sponsors & Collaborators

• Emory University: lead
• AstraZeneca: collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Pakkala S, Higgins K, Chen Z, Sica G, Steuer C, Zhang C, Zhang G, Wang S, Hossain MS, Nazha B, Beardslee T, Khuri FR, Curran W, Lonial S, Waller EK, Ramalingam S, Owonikoko TK. Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study. J Immunother Cancer. 2020 Dec;8(2):e001302. doi: 10.1136/jitc-2020-001302.

  PMID: 33428583 DERIVED

Related Links

• Journal Manuscript

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; Radiation Dose Hypofractionation; Radiosurgery; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Taofeek Owonikoko
• Organization: Emory University

TOWONIK@emory.edu

404-778-5575

Study Officials

• Taofeek Owonikoko, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: March 8, 2016
• Study Start: April 14, 2016
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: June 22, 2021
• Results First Posted: June 22, 2021

Record last verified: 2021-05

Locations

US (2)