MetastaticPhase 1NCT02639026
Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers
A Phase 1 study testing Radiotherapy, MEDI4736 and Tremelimumab in people with Metastatic and Melanoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
The main purpose of this study is to determine how best to combine hypofractionated radiotherapy, MEDI4736, and tremelimumab and to determine how safe and tolerable hypofractionated radiotherapy, MEDI4736, and tremelimumab are when given together in subjects with metastatic, melanoma, non small cell lung cancer… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic, Melanoma, Non Small Cell Lung Cancer (NSCLC)
- What is being tested?
- Radiotherapy, MEDI4736 and Tremelimumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jan 2016to 27 Jun 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically or cytologically confirmed metastatic melanoma,metastatic non-small cell lung cancer, metastatic breast cancer, or metastatic pancreatic adenocarcinoma relapsed or refractory to therapy as outlined below or patients with these malignancies who have declined, are or have become unable to tolerate (e.g. progressive chemotherapy-associated peripheral neuropathy), or were not eligible for standard therapy: Metastatic melanoma patients at any line of therapy, Metastatic non-small cell lung cancer patients who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, including cytotoxic chemotherapy or targeted therapy, Metastatic breast cancer patients who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy, hormonal therapy, or targeted therapy, Metastatic pancreatic adenocarcinoma who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy or targeted therapy
- At least two measurable lesions (including the index lesion) according to RECIST guidelines v1.1
- An index lesion measuring between 1cm - 7cm that is amenable to hypofractionated radiation therapy at the discretion of the treating radiation oncologist
- o Index lesions in the pancreas are excluded in the second cohort
- Age greater than or equal to 18 years
- Signed, written informed consent
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate hematological function documented within 3 weeks prior to initial treatment based on: White blood cell ≥ 2,500 cells/ul without growth factor support, Absolute neutrophil count (ANC) ≥ 1,500 cells/ul without growth factor support, Hemoglobin ≥ 9 g/dL, Platelet count ≥ 100,000 platelets/ul, Adequate hepatic and renal function documented within 3 weeks prior to initial treatment based on: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN). For subjects with liver metastasis, ALT and AST ≤ 5 x ULN, Total bilirubin ≤1.5 x ULN except in patients with documented Gilbert's syndrome or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/dl, Serum creatinine ≤ 2.0 mg/dL
- Full recovery from the acute effects of prior cancer treatments, defined as effects having resolved to NCI CTCAE v4.03 Grade 0 or 1 with the exception of alopecia and certain laboratory values as listed above. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by MEDI4736 and tremelimumab may be included (eg, hearing loss, neuropathy) upon approval of the PI.
- For patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of Day 1 of the study and meet the following criteria:
- At least 28 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or computed tomography (CT) after last day of treatment with radiation to the CNS metastases
- At least 14 days since last dose of corticosteroids
- Must not have leptomeningeal disease or cord compression
- Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of MEDI4736 and tremelimumab. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation for 180 days after the final dose of MEDI4736 and tremelimumab: Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not post-menopausal (defined as 12 months with no menses with postmenopausal gonadotropin levels, luteinizing hormone [LH] and follicle-stimulating [FSH], or postmenopausal estradiol levels within the postmenopausal range according to local guidelines without an alternative medical cause), A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. The acceptable methods of contraception include barrier methods (male condom plus spermicide, Copper T intrauterine device, Levonorgesterel-releasing intrauterine system) or hormonal methods (implants, hormone shot or injection, combined pill, minipill, patch), Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception (as outlined above) from Day 1 through 90 days after receipt of the final dose of MEDI4736 and tremelimumab. In addition, they must refrain from sperm donation for 90 days after the final dose of investigational product.
Who cannot join
- Concurrent enrollment in another clinical study, unless in a follow-up period or the study is an observational or non-interventional study
- Prior treatment with anti-CTLA4, anti-PD-1, or anti-PD-L1 (approved or investigational agent)
- Concurrent treatment with any anticancer agent, including chemotherapy, immunotherapy, or biologic therapy. In breast cancer patients, concurrent use of hormonal therapy (but not trastuzumab) is acceptable provided hormonal therapy was initiated more than 30 days prior to treatment on this study.
- Treatment with any other investigational agent within 3 weeks prior to the first dose of DURVALUMAB (MEDI4736) and tremelimumab
- Any unresolved toxicity NCI CTCAE 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 after consultation with the Study Physician.
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- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician
- Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of DURVALUMAB (MEDI4736) and tremelimumab or still recovering from prior surgery Note: Local surgery of isolated lesions for palliative intent is acceptable
- Current or prior use of immunosuppressive medication within 14 days before the first dose of DURVALUMAB (MEDI4736) and tremelimumab with the exceptions of intranasal and inhaled corticosteroids, systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent, or steroids used transiently to control contrast agent allergies for radiographic studies.
- 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 study physician
- Patients with celiac disease controlled by diet alone.
- History of sensitivity or allergy to monoclonal antibodies or immunoglobulin GActive 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), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). 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
- Receipt of a live, attenuated vaccine within 30 days prior to the first dose of DURVALUMAB (MEDI4736) and tremelimumab Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Clinical contraindication to stereotactic body radiotherapy as determined by the investigator (e.g., active systemic sclerosis, active inflammatory bowel disease if bowel is within radiation field.)
- Prior radiotherapy that precludes the proposed treatment with hypofractionated radiotherapy
- Females who are pregnant, lactating, or intend to become pregnant during the participation of the study
- 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
- Other active invasive malignancy. History of non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast is allowed, as is history of other invasive malignancy that is in remission after treatment with curative intent.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase I Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers
The main purpose of this study is to determine how best to combine hypofractionated radiotherapy, MEDI4736, and tremelimumab and to determine how safe and tolerable hypofractionated radiotherapy, MEDI4736, and tremelimumab are when given together in subjects with metastatic, melanoma, non small cell lung cancer (NSCLC), breast cancer, and pancreatic cancer.
- Conditions
- Metastatic, Melanoma, Non Small Cell Lung Cancer (NSCLC), Breast Cancer, Pancreatic Cancer
- Being tested
- Radiotherapy, MEDI4736, Tremelimumab
- Medical subject headings
- Neoplasm Metastasis, Melanoma, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
two schedules of radiotherapy (8 Gy x 3 fractions and 17 Gy x 1 fraction)
MEDI4736Drug
20 mg/kg MEDI4736 every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses
TremelimumabDrug
1 mg/kg every 4 weeks for 4 doses
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects will receive 20 mg/kg MEDI4736 and 1 mg/kg tremelimumab in combination every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses. The total duration of therapy is 12 months. Cohort 1 tests 8 Gy x 3 fractions Receives: Radiation: Radiotherapy; Drug: MEDI4736; Drug: Tremelimumab |
| Cohort 2 | Experimental | Subjects will receive 20 mg/kg MEDI4736 and 1 mg/kg tremelimumab in combination every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses. The total duration of therapy is 12 months. Cohort 2 tests 17 Gy x 1 fraction. Receives: Radiation: Radiotherapy; Drug: MEDI4736; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2015 (estimated)
- Study start26 Jan 2016
- Primary completion27 Jun 2023
- Study completion27 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MetastaticStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark H. O'Hara, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02639026
- Sponsor's protocol ID
- UPCC 23915
- Status last verified
- Nov 2025
- First submitted
- 21 Dec 2015
- Last updated
- 25 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers
- ClinicalTrials.gov ID
- NCT02639026
- Acronym / sponsor ID
- UPCC 23915
- Conditions
- Metastatic, Melanoma, Non Small Cell Lung Cancer (NSCLC), Breast Cancer, Pancreatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- 26 Jan 2016 (actual)
- Primary completion
- 27 Jun 2023 (actual)
- Study completion
- 27 Jun 2023 (actual)
- First posted
- 24 Dec 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.
The main purpose of this study is to determine how best to combine hypofractionated radiotherapy, MEDI4736, and tremelimumab and to determine how safe and tolerable hypofractionated radiotherapy, MEDI4736, and tremelimumab are when given together in subjects with metastatic, melanoma, non small cell lung cancer (NSCLC), breast cancer, and pancreatic cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Radiation: Radiotherapy, Drug: MEDI4736, Drug: TremelimumabSubjects will receive 20 mg/kg MEDI4736 and 1 mg/kg tremelimumab in combination every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses. The total duration of therapy is 12 months. Cohort 1 tests 8 Gy x 3 fractions |
| Cohort 2 | Experimental | Radiation: Radiotherapy, Drug: MEDI4736, Drug: TremelimumabSubjects will receive 20 mg/kg MEDI4736 and 1 mg/kg tremelimumab in combination every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses. The total duration of therapy is 12 months. Cohort 2 tests 17 Gy x 1 fraction. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with histologically or cytologically confirmed metastatic melanoma,metastatic non-small cell lung cancer, metastatic breast cancer, or metastatic pancreatic adenocarcinoma relapsed or refractory to therapy as outlined below or patients with these malignancies who have declined, are or have become unable to tolerate (e.g. progressive chemotherapy-associated peripheral neuropathy), or were not eligible for standard therapy: Metastatic melanoma patients at any line of therapy, Metastatic non-small cell lung cancer patients who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, including cytotoxic chemotherapy or targeted therapy, Metastatic breast cancer patients who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy, hormonal therapy, or targeted therapy, Metastatic pancreatic adenocarcinoma who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy or targeted therapy
- At least two measurable lesions (including the index lesion) according to RECIST guidelines v1.1
- An index lesion measuring between 1cm - 7cm that is amenable to hypofractionated radiation therapy at the discretion of the treating radiation oncologist
- o Index lesions in the pancreas are excluded in the second cohort
- Age greater than or equal to 18 years
Key exclusion criteria (24 listed)
- Concurrent enrollment in another clinical study, unless in a follow-up period or the study is an observational or non-interventional study
- Prior treatment with anti-CTLA4, anti-PD-1, or anti-PD-L1 (approved or investigational agent)
- Concurrent treatment with any anticancer agent, including chemotherapy, immunotherapy, or biologic therapy. In breast cancer patients, concurrent use of hormonal therapy (but not trastuzumab) is acceptable provided hormonal therapy was initiated more than 30 days prior to treatment on this study.
- Treatment with any other investigational agent within 3 weeks prior to the first dose of DURVALUMAB (MEDI4736) and tremelimumab
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
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 |
|---|---|---|
| Radiotherapytwo schedules of radiotherapy (8 Gy x 3 fractions and 17 Gy x 1 fraction) | Radiation | Cohort 1, Cohort 2 |
| MEDI473620 mg/kg MEDI4736 every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses | Drug | Cohort 1, Cohort 2 |
| Tremelimumab1 mg/kg every 4 weeks for 4 doses | Drug | Cohort 1, Cohort 2 |
Primary outcome
Number of Adverse Events
Time frame: 12 months
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 25 Nov 2025.
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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.
Mark H. O'Hara, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Radiotherapy, MEDI4736 and Tremelimumab in people with Metastatic and Melanoma, run by Abramson Cancer Center at Penn Medicine at 1 site 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 14 inclusion and 24 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 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Number of Adverse Events (time frame: 12 months). 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 25 Nov 2025.