Lung CancerPhase 1NCT02586987
A Study to Assess the Safety, Tolerability and Anti-tumour Activity of Ascending Doses of Selumetinib in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours
A Phase 1 study testing Selumetinib, MEDI4736 and Tremelimumab in people with Lung Cancer and Melanoma, run by AstraZeneca at 6 sites in United States.
Trial summary
This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Lung Cancer, Melanoma, Head and Neck Carcinoma
- What is being tested?
- Selumetinib, MEDI4736 and Tremelimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 6 sitesUnited States
- Study dates
- 28 Dec 2015to 20 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and any locally-required authorization (eg, Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including pre-screening and screening evaluations
- Age ≥18 years at time of study entry
- Histological or cytological confirmation of locally advanced (stage IIIB) or metastatic (stage IV) solid tumours refractory to standard therapy or for which no standard therapy exists
- World Health Organisation Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
- At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated assessment as per Response Evaluation Criteria in Solid Tumours (RECIST criteria v1.1)
- Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures. Females should not be breastfeeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the criteria below at screening.
Show all 12Show fewer
- Postmenopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- Women <50 years old would be considered postmenopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinising hormone (LH) and follicle stimulating hormone (FSH) must also be in the postmenopausal range (as per the institution)
- Documentation of irreversible surgical sterilisation by hysterectomy and / or bilateral oophorectomy and/or bilateral salpingectomy but not tubal ligation
- Male patients should be willing to use barrier contraception ie, condoms plus spermicide
- Mandatory provision of tumour tissue sample available at study entry for exploratory biomarker research. Cytology samples for this exploratory biomarker research will not be acceptable
- Patients must have mCRC and, if MSI status is known, non-high MSI status. MSI status will be evaluated based on previous results of local MSI testing, if available. Patients with known MSI-high status will be excluded; patients with MSS, MSI-low, or unknown MSI status may be enrolled
Who cannot join
- Patients must not enter the study if any of the following exclusion criteria are fulfilled
- Previous enrolment in the present study
- Treatment with any of the following:
- Cytotoxic chemotherapy or other anticancer drugs within 28 days of the 1st dose of study treatment or any investigational agents within 5 half-lives of the product
- MEDI4736 or selumetinib in the present study (ie, dosing with MEDI4736 or selumetinib previously initiated in this study)
- Major surgical procedure, (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the 1st dose of study treatment, or have an anticipated need for major surgery during the study
Show all 52Show fewer
- Palliative radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the 1st dose of study treatment
- Prior exposure to immune-mediated therapy, including, but not limited to, other anti-CTLA- 4 (Cytotoxic T-lymphocyte antigen-4), anti-PD-1 (Programmed cell death 1), anti-PD-L1 (Programmed cell death ligand 1), or anti-PD-L2 (Programmed cell death ligand 2) antibodies, including therapeutic anticancer vaccines
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the medical monitor
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with selumetinib, MEDI4736 or tremelimumab may be included after consultation with the medical monitor
- History of leptomeningeal carcinomatosis and brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT / MRI of the brain prior to study entry
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, irritable bowel disease, or other serious GI (Gastrointestinal) chronic conditions associated with diarrhoea, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [eg, granulomatosis with polyangiitis, Graves' disease; rheumatoid arthritis, hypophysitis, uveitis]) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
- History of active primary immunodeficiency
- Current or prior use of immunosuppressive medication within 14 days before the 1st dose of MEDI4736. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
- As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol or active infection including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) or known history of clinical diagnosis of tuberculosis
- Screening for chronic conditions is not required
- Any of the following cardiac criteria:
- Any factors that increase the risk of QT(ECG interval measured from the onset of the QRS complex to the end of the T wave) interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events (eg, heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age) or mean QTc >470 msec
- Uncontrolled hypertension (eg, BP ≥150/95 mmHg despite medical therapy)
- Acute coronary syndrome within 6 months prior to starting treatment
- Angina Canadian Cardiovascular Society Grade II-IV (despite medical therapy)
- Symptomatic heart failure (New York Heart Association II-IV)
- Prior or current cardiomyopathy
- Baseline LVEF (Left ventricular ejection fraction) <55% measured by echocardiography or MUGA. Appropriate correction to be used if a MUGA is performed.
- Atrial fibrillation with a ventricular rate >100 beats per minute at rest
- Severe valvular heart disease
- Any of the following ophthalmic criteria:
- Current or past history of central serous retinopathy, detachment of retinal pigmented epithelium, or retinal vein occlusion
- Intraocular pressure (IOP) >21 mmHg
- Uncontrolled glaucoma (irrespective of IOP)
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count <1.5 x 109/L
- Platelet count <100 x 109/L
- Haemoglobin <90 g/L
- Alanine aminotransferase >2.5 x ULN (upper limit of normal) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
- Aspartate aminotransferase >2.5 x ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
- Serum bilirubin ≤1.5 x ULN. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia [predominantly unconjugated bilirubin] in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their physician
- Creatinine clearance <50 mL/min (calculated by Cockcroft and Gault equation). Confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
- Refractory nausea and vomiting, chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of selumetinib
- History of hypersensitivity to active or inactive excipients of MEDI4736 or selumetinib or drugs with a similar chemical structure or class to MEDI4736 or selumetinib
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
- Involvement in the planning and conduct of the study (applies to both AZ staff or staff at the study site)
- Previous allogeneic bone marrow transplant
- Body weight <30 kg
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Research Site
Boston, Massachusetts, 02215
Research Site
Charlotte, North Carolina, 28204
Research Site
Chicago, Illinois, 60637
Research Site
Las Vegas, Nevada, 89169-3321
Research Site
New Brunswick, New Jersey, 08901
Research Site
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase I, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability and Preliminary Anti-tumour Activity of Ascending Doses of Selumetinib (AZD6244 Hyd-sulfate) in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours
This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours.
Read the detailed description
This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours refractory to standard therapy or for which no standard therapy exists. The safety, tolerability, and preliminary anti-tumour activity of ascending doses of Selumetinib (AZD6244 Hyd-sulfate) in Combination with MEDI4736 and Selumetinib in Combination with MEDI4736 and Tremelimumab will be investigated. Once safety and tolerability have been established for the relevant dose, expansion cohorts will commence in order to further evaluate safety, tolerability, and provide a preliminary evaluation of the mechanism of action and anti-tumour activity of the drug combination. Mandatory paired biopsy expansion cohorts will be tumour-type specific. Expansion cohorts will open independently for double and triple combination treatments.
- Conditions
- Lung Cancer, Melanoma, Head and Neck Carcinoma, Gastroesophageal Cancer, Breast Cancer, Pancreatic Adenocarcinoma
- Being tested
- Selumetinib, MEDI4736, Tremelimumab
- Keywords
- Selumetinib, Tremelimumab, MEDI4736, Safety, Tolerability, Pharmacokinetics, Patients with advanced solid tumours, Disease progression
- Medical subject headings
- Lung Neoplasms, Melanoma, Breast Neoplasms, Colorectal Neoplasms, Biliary Tract Neoplasms, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
Selumetinib oral
MEDI4736Drug
MEDI4736 IV
TremelimumabDrug
Tremelimumab, IV
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation: Selumetinib+MEDI4736 | Experimental | An oral formulation of selumetinib will be administered in combination with an IV dose of MEDI4736. 4 cohorts of double combination (Selumetinib+MEDI4736).
The decision to escalate to the next dose level/cohort will be made by the Safety Review Committee (SRC) following the completion of the dose limiting toxicity (DLT) assessment period for at least 3 evaluable patients in each cohort. Receives: Drug: Selumetinib; Drug: MEDI4736 |
| Mandatory paired biopsy expansion cohort: Selumetinib+MEDI4736 | Experimental | One or more independent mandatory paired biopsy expansion cohorts for double combination treatment will start after safety and tolerability have been established for the relevant dose. It will be tumour-type specific for double combination, the tumor type will be determined from emerging data. Receives: Drug: Selumetinib; Drug: MEDI4736 |
| Dose escalation: Selumetinib+MEDI4736+tremelimumab | Experimental | An oral formulation of selumetinib will be administered in combination with an IV dose of MEDI4736 and an IV dose of tremelimumab.
For triple combination treatment, the starting dose of selumetinib (DL1) will be determined by the SRC based on emerging data from dose escalation cohorts of double combination treatment. Receives: Drug: Selumetinib; Drug: MEDI4736; Drug: Tremelimumab |
| Mandatory paired biopsy expansion cohort: triple combination | Experimental | One or more independent mandatory paired biopsy expansion cohorts for triple combination treatment will start after safety and tolerability have been established for the relevant dose. It will be tumour-type specific for triple combination, the tumor type will be determined from emerging data. Receives: Drug: Selumetinib; Drug: MEDI4736; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Adverse Events
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of safety laboratory tests
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of blood pressure (BP)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Electrocardiogram (ECG)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of physical examinations
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Echocardiogram (ECHO)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of pulse
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of body temperature
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of respiratory rate
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Multigated Acquisition (MUGA)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (best corrected visual acuity)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (Intraocular pressure)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (slit lamp fundoscopy)
Measured: From screening until approximately 30 days after last dose of study drug at disease progression
Secondary outcomes (8)
Long-term tolerated dose and exposure predicted to result in biological activity (including but not limited to Response Evaluation Criteria in Solid Tumours (RECIST)
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Objective response rate (ORR)
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Change in tumour size
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Best Objective Response (BoR)
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Duration of Response (DoR)
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Progression-free survival (PFS)
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Overall survival (OS)
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
MEDI4736 and/or tremelimumab anti-drug antibody (ADA) level in Plasma
Measured: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study start28 Dec 2015
- Primary completion25 Jul 2018
- Study completion20 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pasi A. Jänne, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02586987
- Sponsor's protocol ID
- D1345C00003
- Status last verified
- Nov 2019
- First submitted
- 21 Sep 2015
- Last updated
- 18 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability and Preliminary Anti-tumour Activity of Ascending Doses of Selumetinib (AZD6244 Hyd-sulfate) in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT02586987
- Acronym / sponsor ID
- D1345C00003
- Conditions
- Lung Cancer, Melanoma, Head and Neck Carcinoma, Gastroesophageal Cancer, Breast Cancer, Pancreatic Adenocarcinoma
- Keywords
- Selumetinib, Tremelimumab, MEDI4736, Safety, Tolerability, Pharmacokinetics, Patients with advanced solid tumours, Disease progression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 28 Dec 2015 (actual)
- Primary completion
- 25 Jul 2018 (actual)
- Study completion
- 20 Sep 2019 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours.
Detailed description
This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours refractory to standard therapy or for which no standard therapy exists. The safety, tolerability, and preliminary anti-tumour activity of ascending doses of Selumetinib (AZD6244 Hyd-sulfate) in Combination with MEDI4736 and Selumetinib in Combination with MEDI4736 and Tremelimumab will be investigated. Once safety and tolerability have been established for the relevant dose, expansion cohorts will commence in order to further evaluate safety, tolerability, and provide a preliminary evaluation of the mechanism of action and anti-tumour activity of the drug combination. Mandatory paired biopsy expansion cohorts will be tumour-type specific. Expansion cohorts will open independently for double and triple combination treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose escalation: Selumetinib+MEDI4736 | Experimental | Drug: Selumetinib, Drug: MEDI4736An oral formulation of selumetinib will be administered in combination with an IV dose of MEDI4736. 4 cohorts of double combination (Selumetinib+MEDI4736). The decision to escalate to the next dose level/cohort will be made by the Safety Review Committee (SRC) following the completion of the dose limiting toxicity (DLT) assessment period for at least 3 evaluable patients in each cohort. |
| Mandatory paired biopsy expansion cohort: Selumetinib+MEDI4736 | Experimental | Drug: Selumetinib, Drug: MEDI4736One or more independent mandatory paired biopsy expansion cohorts for double combination treatment will start after safety and tolerability have been established for the relevant dose. It will be tumour-type specific for double combination, the tumor type will be determined from emerging data. |
| Dose escalation: Selumetinib+MEDI4736+tremelimumab | Experimental | Drug: Selumetinib, Drug: MEDI4736, Drug: TremelimumabAn oral formulation of selumetinib will be administered in combination with an IV dose of MEDI4736 and an IV dose of tremelimumab. For triple combination treatment, the starting dose of selumetinib (DL1) will be determined by the SRC based on emerging data from dose escalation cohorts of double combination treatment. |
| Mandatory paired biopsy expansion cohort: triple combination | Experimental | Drug: Selumetinib, Drug: MEDI4736, Drug: TremelimumabOne or more independent mandatory paired biopsy expansion cohorts for triple combination treatment will start after safety and tolerability have been established for the relevant dose. It will be tumour-type specific for triple combination, the tumor type will be determined from emerging data. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent and any locally-required authorization (eg, Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including pre-screening and screening evaluations
- Age ≥18 years at time of study entry
- Histological or cytological confirmation of locally advanced (stage IIIB) or metastatic (stage IV) solid tumours refractory to standard therapy or for which no standard therapy exists
- World Health Organisation Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
- At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated assessment as per Response Evaluation Criteria in Solid Tumours (RECIST criteria v1.1)
Key exclusion criteria (52 listed)
- Patients must not enter the study if any of the following exclusion criteria are fulfilled
- Previous enrolment in the present study
- Treatment with any of the following:
- Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- History of leptomeningeal carcinomatosis and brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT / MRI of the brain prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelumetinibSelumetinib oral | Drug | Dose escalation: Selumetinib+MEDI4736, Dose escalation: Selumetinib+MEDI4736+tremelimumab, Mandatory paired biopsy expansion cohort: Selumetinib+MEDI4736, Mandatory paired biopsy expansion cohort: triple combination |
| MEDI4736MEDI4736 IV | Drug | Dose escalation: Selumetinib+MEDI4736, Dose escalation: Selumetinib+MEDI4736+tremelimumab, Mandatory paired biopsy expansion cohort: Selumetinib+MEDI4736, Mandatory paired biopsy expansion cohort: triple combination |
| TremelimumabTremelimumab, IV | Drug | Dose escalation: Selumetinib+MEDI4736+tremelimumab, Mandatory paired biopsy expansion cohort: triple combination |
Primary outcome
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Adverse Events
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of safety laboratory tests
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of blood pressure (BP)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Electrocardiogram (ECG)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of physical examinations
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Echocardiogram (ECHO)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of pulse
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of body temperature
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of respiratory rate
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Multigated Acquisition (MUGA)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (best corrected visual acuity)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (Intraocular pressure)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (slit lamp fundoscopy)
Time frame: From screening until approximately 30 days after last dose of study drug at disease progression
8 secondary outcomes
Long-term tolerated dose and exposure predicted to result in biological activity (including but not limited to Response Evaluation Criteria in Solid Tumours (RECIST)
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Objective response rate (ORR)
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Change in tumour size
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Best Objective Response (BoR)
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Duration of Response (DoR)
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Progression-free survival (PFS)
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Overall survival (OS)
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
MEDI4736 and/or tremelimumab anti-drug antibody (ADA) level in Plasma
Time frame: From screening until 30 days after last dose of study drug at disease progression, approximately 6 months however there is no maximum duration of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
Related trials for Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pasi A. Jänne, MD, PhD principal investigator
Dana-Farber Cancer Institute
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selumetinib, MEDI4736 and Tremelimumab in people with Lung Cancer and Melanoma, run by AstraZeneca at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Adverse Events (time frame: From screening until approximately 30 days after last dose of study drug at disease progression). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.