Staggered Chemo-Immunotherapy With Durvalumab MEDI4736 Pemetrexed & Carboplatin (PC) for Metastatic Non-Squamous NSCLC

  • STATUS
    Recruiting
  • End date
    Feb 15, 2026
  • participants needed
    84
  • sponsor
    University of Utah
Updated on 28 June 2021
platelet count
cancer
measurable disease
gilbert's syndrome
metastasis
pemetrexed
neutrophil count
carboplatin
durvalumab

Summary

This is a Phase II, open label, randomized study of durvalumab in combination with pemetrexed and carboplatin in eligible adult patients with locally advanced or metastatic non-small cell lung cancer. The study will focus on the efficacy of two alternative staggered dosing regimens.

Description

This trial will evaluated two different schedules of concurrent chemoimmunotherapy while simultaneously measuring immune activation, immune resistance and host factors. Both arms will consist of concurrent chemoimmunotherapy with durvalumab, pemetrexed and carboplatin, but in arm 1 the chemotherapy will precede the immunotherapy by a week and in arm 2 the immunotherapy will precede the chemotherapy by a week. Staggering these therapies still allows concurrent administration while allowing some degree of temporal isolation to better understand the contributions by chemotherapy and immunotherapy in this setting. Host and laboratory factors will be measured during treatment. We hypothesize that staggered dosing of immunotherapy in combination with chemotherapy can improve clinical benefit.

Details
Condition Non Small Cell Lung Cancer Metastatic
Treatment carboplatin, Pemetrexed, durvalumab
Clinical Study IdentifierNCT04163432
SponsorUniversity of Utah
Last Modified on28 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female subject aged 18 years
Histologically or cytologically confirmed metastatic non-squamous non-small cell lung cancer
Patient has measurable disease as defined by RECIST 1.1 as assessed by either CT or MRI
Chemoimmunotherapy nave (including durvalumab)
ECOG Performance Status 2
\--Note: If performance status = 2, ensure that there is a slot available
prior to registration as only 20 PS = 2 patients will be enrolled on the
protocol
Must have a life expectancy of at least 12 weeks
Adequate organ function as defined as
Hematologic
White blood cell count > 2.0 g/dL
Platelet count 100,000/mm3
Hemoglobin 9 g/dL
Absolute neutrophil count (ANC) 1,500/mm3
Hepatic
Total Bilirubin 1.5 x institutional upper limit of normal (ULN)
Except for patients with Gilbert's syndrome
AST(SGOT)/ALT(SGPT) 2.5 institutional ULN or 5 institutional ULN if liver metastases are present
Renal
eGFR 30 mL/min/1.73m2 or creatinine clearance 30 mL/min by Cockcroft-Gault
Males: ((140-age)weight[kg])/(serum creatinine [mg/dL]72)
Females: (((140-age)weight[kg])/(serum creatinine [mg/dL]72))0.85
Concurrent enrollment in the study, "Rethinking Measurement of Performance Status in Cancer Patients," IRB 112529
Concurrent enrollment in the study, "An Observational Study Assessing the Clinical Effectiveness of the VeriStrat Test and Validating Immunotherapy Tests in Subjects with Non-Small Cell Lung Cancer," IRB 100314
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply
Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Women 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Highly effective contraception for both male and female subjects throughout the study and for at least 3 months after the last dose of study therapy
Recovery to baseline or Grade 1 CTCAE v.5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
Patient 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
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations

Exclusion Criteria

ALK or EGFR non-squamous non-small cell lung cancer
Prior radiation therapy within 2 weeks prior to cycle one day one
Exception: Prior palliative radiotherapy is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP
Note: Local surgery of isolated lesions for palliative intent is acceptable
History of allogenic organ transplantation
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the principal investigator
Patients with celiac disease controlled by diet alone
Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids
\--Intranasal, inhaled, topical steroids, eye drops or local steroid injection
(eg,intra-articular injection)
Systemic corticosteroids at physiologic doses 10mg/day of prednisone or equivalent
Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication)
History of active primary immunodeficiency
Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, and low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration) or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms is allowed
Uncontrolled CNS metastases; subjects with previously treated brain metastases will be allowed if the brain metastases have been treated, toxicities have resolved to grade 1 or baseline and steroids are no longer required
\--Patients with asymptomatic brain metastasis are allowed if previous steroid
treatment was discontinued 6 weeks
History of leptomeningeal carcinomatosis
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment
Note: Patients on effective anti-retroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial
Active infection including: tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C
Note: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
Vaccination with a live vaccine within 30 days of cycle one day one and while on trial is prohibited except for administration of inactivated vaccines
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies, cisplatin, other platinum-containing compounds, or mannitol. (NCI CTCAE v5.0 Grade 3)
Subjects taking prohibited medications as described in Section 6.5.2. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note