Breast NeoplasmsPhase 1NCT02309177
Safety Study of Nivolumab With Nab-Paclitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-Paclitaxel / Carboplatin in Stage IIIB/IV Non-Small Cell Lung Cancer or Nab-Paclitaxel in Recurrent Metastatic Breast Cancer
A Phase 1 study testing nab-Paclitaxel, Nivolumab and Gemcitabine in people with Breast Neoplasms and Pancreatic Neoplasms, run by Celgene at 15 sites in United States.
Trial summary
The purpose of this study is to assess safety of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, Non Small Cell Lung Cancer (NSCLC) and Metastatic Breast Cancer (mBC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms, Pancreatic Neoplasms
- What is being tested?
- nab-Paclitaxel, Nivolumab and Gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 15 sitesUnited States
- Study dates
- 12 Jan 2015to 12 Sep 2018
- 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
- Subject is male or female, ≥ 18 years old at the time of signing the informed consent form (ICF).
- Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:
- Pancreatic Cancer
- Subject has a definitive histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas. Subjects with islet cell neoplasms are excluded.
- nab-Paclitaxel and Nivolumab: Subjects must have received 1 prior systemic chemotherapy regimen for locally advanced or metastatic disease.
- nab-Paclitaxel + Nivolumab and nab-paclitaxel, Gemcitabine and Nivolumab: Subjects must have received no previous systemic chemotherapy or investigational therapy for the treatment of pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy, with the exception of prior treatment administered as a radiosensitizer concomitant with radiotherapy in the adjuvant setting. In this case, ≥ 6 months must have elapsed since completion of the last dose and no lingering toxicities may be present. Initial diagnosis of metastatic disease must have occurred ≤ 6 weeks prior to randomization in the study.
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- Non-small Cell Lung Cancer (NSCLC):
- Subject has definitive histologically or cytologically confirmed Stage IIIB or IV NSCLC.
- Subjects must have received no previous chemotherapy or investigational therapy for the treatment of metastatic disease. Adjuvant, neo-adjuvant chemotherapy or chemoradiotherapy is permitted providing cytotoxic chemotherapy was completed > 12 months prior to randomization, without disease recurrence or progression during those 12 months.
- Metastatic Breast Cancer: Human Epidermal Growth Factor Receptor 2 - negative (HER2(-)) recurrent Metastatic Breast Cancer:
- Subject has a definitive histologically or cytologically confirmed diagnosis of HER2(-) metastatic breast cancer.
- Subject has received zero to one prior cytotoxic chemotherapy regimen for metastatic disease, regardless of prior targeted therapy (eg. everolimus, palbociclib or lapatinib), biologic (eg. trastuzumab) or hormonal therapy treatment (eg. aromatase inhibitors, selective estrogen receptor modulators, or estrogen receptor down-regulators).
- If subject has received solvent-based paclitaxel (TAXOL) or docetaxel as adjuvant chemotherapy, subject must not have relapsed with breast cancer within 12 months of completing said therapy.
- Suitable candidate for single agent nab-paclitaxel as assessed by the investigator.
- 3. Subject has measurable disease according to RECIST 1.1. 4. Archival formalin-fixed, paraffin-embedded tumor sample collected within 90 days prior to subject consent available or subject has biopsiable metastatic lesion and is willing to undergo biopsy .
- 5. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- 6. Subject has no other malignancy within 5 years, except non-melanoma skin cancer, cervical intraepithelial neoplasia, or in-situ cervical cancer or incidental histological finding of prostate cancer (TNM stage of T1a or T1b); all treatments of which should have been completed 6 months prior to signing ICF.
- 7. Subject has the following laboratory values at screening:
- WBCs ≥ 2000/uL,
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
- Hemoglobin (Hgb) ≥ 90 g/L,
- Platelets (plt) ≥ 100 x 109/L,
- Potassium within normal range, or correctable with supplements,
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 3.0 x ULN if liver tumor is present,
- Serum total bilirubin ≤ 1.5 x ULN (except in subjects with Gilbert's who may have serum bilirubin < 3.0 x ULN),
- Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60 mL/min,
- Normal coagulation [prothrombin time and partial thromboplastin time within normal limits (±15%)].
- 8. Subject has resting baseline oxygen saturation by pulse oximetry of ≥ 92% at rest.
- 9. Females of child-bearing potential (defined as a sexually mature woman who: 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months) must:
- Agree in writing to use two forms of medical doctor-approved contraception throughout the study (without interruptions while on study treatment) and subsequently for 23 weeks5 months.
- Have a negative serum pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of β hCG) at screening and 24 hours prior to the start of any IP and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
- 10. Male subjects agree in writing to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 7 months following IP discontinuation, even if he has undergone a successful vasectomy.
- 11. Subject or his/her legally authorized representative or guardian understands and voluntarily signs an informed consent document prior to any study related assessments/procedures are conducted (except as noted in Section 6).
- 12. Subject is able to adhere to the study visit schedule and other protocol requirements.
Who cannot join
- Subject has a history of allergy or hypersensitivity to any study drugs or their excipients.
- Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
- Subject has symptomatic brain metastases, spinal cord compression, or intractable back pain due to compression of destructive mass.
- Subject has active, known or suspected autoimmune disease, including systemic lupus erythematodes, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or auto-immune hepatitis. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subject is currently receiving or requires treatment with immunosuppressive agents or immunosuppressive doses of systemic corticosteroids (unless used to treat drug-related adverse events).Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption), and some uses of systemic corticosteroids are permitted as per Section 9.1.
- Subject has any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events ) Grade 2 at randomization/enrollment.
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- Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Subject has a high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
- Subject has unstable angina, a significant cardiac arrhythmia, or New York Heart Association Class 3 or 4 congestive heart failure.
- Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's disease).
- Subject has had major surgery, other than diagnostic surgery, within 4 weeks prior to treatment in study.
- Subject has known acute or chronic pancreatitis.
- Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ≥ NCI CTCAE Grade 2, despite medical management.
- Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Subject has any history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS).
- Subject has active hepatitis B or C. Subject with hepatitis in medical history may be eligible if infection considered cleared, ie core Ab+, surface Ab+, surface Ag- for hep B and Ab+/DNA- for hep C.
- Subject is pregnant or breast-feeding. Women must not breast-feed until at 5 months after completion of study participation..
- Subject is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug.
- Subject is currently using or use within 6 months of illicit drugs.
- Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Subject has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Subject has any condition that confounds the ability to interpret data from the study.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Dana-Farber / Harvard Cancer Institute
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Levine Cancer Institute
Charlotte, North Carolina, 28204
Northwestern University-NMDTI
Chicago, Illinois, 60611
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45242
Ohio State Medical Center
Columbus, Ohio, 43210
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Regional Care Cancer Centers NJ
Morristown, New Jersey, 79062
Yale Cancer Center
New Haven, Connecticut, 06510
University of Pennslyvania
Philadelphia, Pennsylvania, 19104
UC Davis Cancer Center
Sacramento, California, 95817
University of California Los Angeles
Santa Monica, California, 90404
Seattle Cancer Center Alliance
Seattle, Washington, 98109
H. Lee Moffitt Cancer Center and Research Institute University of South Florida
Tampa, Florida, 33612
About this study
Official title: A Phase 1, Open-label, Multicenter, Safety Study of Nivolumab (Bms-936558) in Combination With Nab-pacitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-paclitaxel/Carboplatin in Stage Iiib/iv Non-small Cell Lung Cancer or Nab-paclitaxel in Metastastic Breast Cancer
The purpose of this study is to assess safety of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, Non Small Cell Lung Cancer (NSCLC) and Metastatic Breast Cancer (mBC).
Read the detailed description
This will be a phase 1, open-label, multicenter, safety study of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, NSCLC and mBC. This is a six arm study assessing two treatment arms per tumor-type/indication:
- Adenocarcinoma of the pancreas with 1 prior systemic chemotherapy (Arm A, Part 1 only); and subsequently no prior chemotherapy, surgery or radiation therapy for locally advanced or metastatic disease (Arm A, Part 2 and Arm B):
- Panc Ca Arm A: nab-paclitaxel with nivolumab starting at Cycle 1.
- Panc Ca Arm B: nab-paclitaxel/gemcitabine with nivolumab starting at Cycle 1.
- Stage IIIB or IV NSCLC with no prior chemotherapy for metastatic disease and who are not candidates for curative surgery or radiation:
- NSCLC Arm C: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle 1 and continuing as monotherapy starting at Cycle 5.
- NSCLC Arm D: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle 3 and continuing as monotherapy starting at Cycle 5
- HER2-negative recurrent metastatic breast cancer after one prior regimen for mBC, including an anthracycline unless clinically contraindicated:
- mBC Arm E: weekly nab-paclitaxel with nivolumab starting at Cycle 3.
- mBC Arm F: q3weekly nab-paclitaxel with nivolumab starting at Cycle 3. Enrollment in each treatment arm will be conducted in two sequential parts to allow for the evaluation of the DLT in Part 1 prior to expanding the treatment arm in Part 2.
Part 1:
Part 1 will assess the Dose Limiting Toxicity (DLT) of the nivolumab dose in combination with nab-paclitaxel regimens in each treatment arm.
Subjects who meet the entry criteria will be assigned to the respective treatment arm based on tumor type and indication as outlined above. Panc Ca Arms A and B, as well as NSCLC Arms C and D, will enroll sequentially in Part 1. The safety of nivolumab in combination with nabpaclitaxel, without gemcitabine, will first be assessed in Arm A in subjects with one prior systemic chemotherapy regimen for locally advanced or metastatic disease. Panc Ca Arm B may begin enrolling subjects in Part 1, if Panc Ca Arm A is deemed safe, based on DLT criteria. Similarly, NSCLC Arm D will begin to enroll in Part 1 after NSCLC Arm C is deemed safe to expand in Part 2. However, Arm D may be initiated, even if Arm C is not to proceed for Part 2, if the totality of data from Arm C and emerging data from this and other studies in NSCLC with nivolumab in combination with platinum chemotherapy doublets support the decision. Unlike the Panc Ca and NSCLC arms, the two mBC arms (Arms E and F) will be initiated simultaneously. Subjects will be assigned randomly between treatment arms of a tumor type/indication whenever both treatment arms are enrolling. An IRT system will be used to ensure the central random allocation of subjects.
Part 2:
Treatment arms deemed safe within each tumor-type/indication may be expanded using the RP2D with an additional approximately 14 subjects (to attain a total of 20 nivolumab-treated subjects) to further assess safety and tolerability, as well as explore anti-tumor activity of the proposed regimens. Since the primary population for the pancreas arms is in subjects with no prior chemotherapy, surgery or radiation therapy, enrollment in Part 2 for Panc Ca Arm A will continue until 20 such subjects have been treated with at least one dose of nivolumab. Additionally, in Parts 1 and 2 overall, each mBC Arm (E and F) will enroll a minimum of 9 subjects with triple- negative breast cancer (TNBC), treated at the RP2D.
For both Part 1 and 2, subjects may continue to receive their assigned treatment regimen until Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined progression or until unacceptable toxicity. However, the chemotherapy doublet will only be given for 4 cycles in the NSCLC arms; thereafter, nivolumab will be given as monotherapy.
- Conditions
- Breast Neoplasms, Pancreatic Neoplasms
- Being tested
- nab-Paclitaxel, Nivolumab, Gemcitabine, Carboplatin
- Keywords
- Pancreatic Cancer, Breast Cancer, Metastatic Breast Cancer, nab-Paclitaxel, Gemcitabine, Carboplatin, Non-Small Cell Lung Cancer, Lung Cancer, mBC, NSCLC, Triple-negative Breast Cancer, Hormone Receptor Positive, ER+, PR+, TNBC, Nivolumab, PD-1, Check-point Inhibitor/s, Immune Check-point Inhibitor/s, Anti-PD-1
- Medical subject headings
- Breast Neoplasms, Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nab-PaclitaxelDrug
Also called Abraxane
NivolumabDrug
Also called BMS-936558 or MDX1106
GemcitabineDrug
Also called Gemzar
CarboplatinDrug
Also called Paraplatin
| Study group | Role | What they receive |
|---|---|---|
| nab-Paclitaxel and Nivolumab in Pancreatic Cancer | Experimental | nab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28 day cycle. Receives: Drug: nab-Paclitaxel; Drug: Nivolumab |
| nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer | Experimental | nab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, gemcitabine 1000 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28-day cycle. Receives: Drug: nab-Paclitaxel; Drug: Nivolumab; Drug: Gemcitabine |
| nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC | Experimental | nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 (Cycles 1 to 4 only) of each 21 day cycle; nivolumab on Day 15 of each 21 day cycle starting in Cycle 1. Receives: Drug: nab-Paclitaxel; Drug: Nivolumab; Drug: Carboplatin |
| nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC | Experimental | nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 (Cycles 1 to 4 only) of each 21 day cycle; nivolumab on Day 15 of each 21 day cycle starting in Cycle 3. Receives: Drug: nab-Paclitaxel; Drug: Nivolumab; Drug: Carboplatin |
| nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC | Experimental | nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 28 day cycle, plus nivolumab on Days 1 and 15 starting in Cycle 3. Receives: Drug: nab-Paclitaxel; Drug: Nivolumab |
| nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC | Experimental | nab-paclitaxel 260 mg/m2 on Days 1 of each 21 day cycle, plus nivolumab on Days 15 starting in Cycle 3. Receives: Drug: nab-Paclitaxel; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate Dose Limiting Toxicity (DLT) of each combination regimen
The number of subjects with dose limiting toxicity in each treatment arm in Part 1.
Measured: 24 months
Evaluate the safety of the nab-paclitaxel/nivolumab combination regimens
The percentage of subjects with Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) or treatment discontinuation due to a TEAE during the study
Measured: 44 months
Grade 3 or 4 TEAE
The percentage of subjects with Grade 3 or 4 TEAEs or treatment discontinuation due to a TEAE during the study.
Measured: 44 months
Secondary outcomes (6)
Treatment Emergent Adverse Events
TEAEs leading to dose reduction, delay, interruption or treatment discontinuation
Measured: 44 months
Progression-free survival
Progression-free survival, which is defined as the time from the date of first dose of any IP to the date of disease progression or death (any cause) on or prior to the data cutoff date for analyses.
Measured: 44 months
Overall Survival
Overall survival is defined as the time between the first dose of any IP and death.
Measured: 44 months
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiographically assessed complete response, partial response, or stable disease as determined by the investigator according to RECIST 1.1 guidelines.
Measured: 44 Months
Overall Response Rate
Overall response rate is defined as the percent of subjects who have a radiographically assessed complete or partial response as determined by the investigator according to RECIST 1.1 guidelines.
Measured: 44 Months
Duration of Response
The duration of overall response is measured from the time measurement criteria are met, based on RECIST 1.1 guidelines, for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measured: 44 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2014 (estimated)
- Study start12 Jan 2015
- Primary completion12 Sep 2018
- Study completion12 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by CelgeneThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chrystal Louis, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02309177
- Sponsor's protocol ID
- ABI-007-ST-001
- Status last verified
- May 2019
- First submitted
- 3 Dec 2014
- Last updated
- 31 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Goldman JW, Waterhouse DM, George B, O'Dwyer PJ, Bhore R, Banerjee S, Lyons L, Louis CU, Ong TJ, Kelly K. Safety and Efficacy Results of a Phase I, Open-Label Study of Concurrent and Delayed Nivolumab in Combination With nab-Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer. Front Oncol. 2019 Nov 26;9:1256. doi: 10.3389/fonc.2019.01256. eCollection 2019.
PubMed 31850192
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Multicenter, Safety Study of Nivolumab (Bms-936558) in Combination With Nab-pacitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-paclitaxel/Carboplatin in Stage Iiib/iv Non-small Cell Lung Cancer or Nab-paclitaxel in Metastastic Breast Cancer
- ClinicalTrials.gov ID
- NCT02309177
- Acronym / sponsor ID
- ABI-007-ST-001
- Conditions
- Breast Neoplasms, Pancreatic Neoplasms
- Keywords
- Pancreatic Cancer, Breast Cancer, Metastatic Breast Cancer, nab-Paclitaxel, Gemcitabine, Carboplatin, Non-Small Cell Lung Cancer, Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 12 Jan 2015 (actual)
- Primary completion
- 12 Sep 2018 (actual)
- Study completion
- 12 Sep 2018 (actual)
- First posted
- 5 Dec 2014 (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 purpose of this study is to assess safety of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, Non Small Cell Lung Cancer (NSCLC) and Metastatic Breast Cancer (mBC).
Detailed description
This will be a phase 1, open-label, multicenter, safety study of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, NSCLC and mBC. This is a six arm study assessing two treatment arms per tumor-type/indication:
- Adenocarcinoma of the pancreas with 1 prior systemic chemotherapy (Arm A, Part 1 only); and subsequently no prior chemotherapy, surgery or radiation therapy for locally advanced or metastatic disease (Arm A, Part 2 and Arm B):
- Panc Ca Arm A: nab-paclitaxel with nivolumab starting at Cycle 1.
- Panc Ca Arm B: nab-paclitaxel/gemcitabine with nivolumab starting at Cycle 1.
- Stage IIIB or IV NSCLC with no prior chemotherapy for metastatic disease and who are not candidates for curative surgery or radiation:
- NSCLC Arm C: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle 1 and continuing as monotherapy starting at Cycle 5.
- NSCLC Arm D: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle 3 and continuing as monotherapy starting at Cycle 5
- HER2-negative recurrent metastatic breast cancer after one prior regimen for mBC, including an anthracycline unless clinically contraindicated:
- mBC Arm E: weekly nab-paclitaxel with nivolumab starting at Cycle 3.
- mBC Arm F: q3weekly nab-paclitaxel with nivolumab starting at Cycle 3. Enrollment in each treatment arm will be conducted in two sequential parts to allow for the evaluation of the DLT in Part 1 prior to expanding the treatment arm in Part 2.
Part 1:
Part 1 will assess the Dose Limiting Toxicity (DLT) of the nivolumab dose in combination with nab-paclitaxel regimens in each treatment arm.
Subjects who meet the entry criteria will be assigned to the respective treatment arm based on tumor type and indication as outlined above. Panc Ca Arms A and B, as well as NSCLC Arms C and D, will enroll sequentially in Part 1. The safety of nivolumab in combination with nabpaclitaxel, without gemcitabine, will first be assessed in Arm A in subjects with one prior systemic chemotherapy regimen for locally advanced or metastatic disease. Panc Ca Arm B may begin enrolling subjects in Part 1, if Panc Ca Arm A is deemed safe, based on DLT criteria. Similarly, NSCLC Arm D will begin to enroll in Part 1 after NSCLC Arm C is deemed safe to expand in Part 2. However, Arm D may be initiated, even if Arm C is not to proceed for Part 2, if the totality of data from Arm C and emerging data from this and other studies in NSCLC with nivolumab in combination with platinum chemotherapy doublets support the decision. Unlike the Panc Ca and NSCLC arms, the two mBC arms (Arms E and F) will be initiated simultaneously. Subjects will be assigned randomly between treatment arms of a tumor type/indication whenever both treatment arms are enrolling. An IRT system will be used to ensure the central random allocation of subjects.
Part 2:
Treatment arms deemed safe within each tumor-type/indication may be expanded using the RP2D with an additional approximately 14 subjects (to attain a total of 20 nivolumab-treated subjects) to further assess safety and tolerability, as well as explore anti-tumor activity of the proposed regimens. Since the primary population for the pancreas arms is in subjects with no prior chemotherapy, surgery or radiation therapy, enrollment in Part 2 for Panc Ca Arm A will continue until 20 such subjects have been treated with at least one dose of nivolumab. Additionally, in Parts 1 and 2 overall, each mBC Arm (E and F) will enroll a minimum of 9 subjects with triple- negative breast cancer (TNBC), treated at the RP2D.
For both Part 1 and 2, subjects may continue to receive their assigned treatment regimen until Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined progression or until unacceptable toxicity. However, the chemotherapy doublet will only be given for 4 cycles in the NSCLC arms; thereafter, nivolumab will be given as monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| nab-Paclitaxel and Nivolumab in Pancreatic Cancer | Experimental | Drug: nab-Paclitaxel, Drug: Nivolumabnab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28 day cycle. |
| nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer | Experimental | Drug: nab-Paclitaxel, Drug: Nivolumab, Drug: Gemcitabinenab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, gemcitabine 1000 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28-day cycle. |
| nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC | Experimental | Drug: nab-Paclitaxel, Drug: Nivolumab, Drug: Carboplatinnab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 (Cycles 1 to 4 only) of each 21 day cycle; nivolumab on Day 15 of each 21 day cycle starting in Cycle 1. |
| nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC | Experimental | Drug: nab-Paclitaxel, Drug: Nivolumab, Drug: Carboplatinnab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 (Cycles 1 to 4 only) of each 21 day cycle; nivolumab on Day 15 of each 21 day cycle starting in Cycle 3. |
| nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC | Experimental | Drug: nab-Paclitaxel, Drug: Nivolumabnab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 28 day cycle, plus nivolumab on Days 1 and 15 starting in Cycle 3. |
| nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC | Experimental | Drug: nab-Paclitaxel, Drug: Nivolumabnab-paclitaxel 260 mg/m2 on Days 1 of each 21 day cycle, plus nivolumab on Days 15 starting in Cycle 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Subject is male or female, ≥ 18 years old at the time of signing the informed consent form (ICF).
- Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:
- Non-small Cell Lung Cancer (NSCLC):
- Subjects must have received no previous chemotherapy or investigational therapy for the treatment of metastatic disease. Adjuvant, neo-adjuvant chemotherapy or chemoradiotherapy is permitted providing cytotoxic chemotherapy was completed > 12 months prior to randomization, without disease recurrence or progression during those 12 months.
- Metastatic Breast Cancer: Human Epidermal Growth Factor Receptor 2 - negative (HER2(-)) recurrent Metastatic Breast Cancer:
Key exclusion criteria (22 listed)
- Subject has a history of allergy or hypersensitivity to any study drugs or their excipients.
- Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
- Subject has symptomatic brain metastases, spinal cord compression, or intractable back pain due to compression of destructive mass.
- Subject has active, known or suspected autoimmune disease, including systemic lupus erythematodes, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or auto-immune hepatitis. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subject is currently receiving or requires treatment with immunosuppressive agents or immunosuppressive doses of systemic corticosteroids (unless used to treat drug-related adverse events).Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption), and some uses of systemic corticosteroids are permitted as per Section 9.1.
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 |
|---|---|---|
| nab-PaclitaxelAlso: Abraxane | Drug | nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC, nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC, nab-Paclitaxel and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC, nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC |
| NivolumabAlso: BMS-936558 or MDX1106 | Drug | nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC, nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC, nab-Paclitaxel and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC, nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC |
| GemcitabineAlso: Gemzar | Drug | nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer |
| CarboplatinAlso: Paraplatin | Drug | nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC, nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC |
Primary outcome
Evaluate Dose Limiting Toxicity (DLT) of each combination regimen
Time frame: 24 months
The number of subjects with dose limiting toxicity in each treatment arm in Part 1.
Evaluate the safety of the nab-paclitaxel/nivolumab combination regimens
Time frame: 44 months
The percentage of subjects with Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) or treatment discontinuation due to a TEAE during the study
Grade 3 or 4 TEAE
Time frame: 44 months
The percentage of subjects with Grade 3 or 4 TEAEs or treatment discontinuation due to a TEAE during the study.
6 secondary outcomes
Treatment Emergent Adverse Events
Time frame: 44 months
Progression-free survival
Time frame: 44 months
Overall Survival
Time frame: 44 months
Disease Control Rate
Time frame: 44 Months
Overall Response Rate
Time frame: 44 Months
Duration of Response
Time frame: 44 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 31 May 2019.
- Derived from this study: PubMed 31850192Goldman JW, Waterhouse DM, George B, O'Dwyer PJ, Bhore R, Banerjee S, Lyons L, Louis CU, Ong TJ, Kelly K. Safety and Efficacy Results of a Phase I, Open-Label Study of Concurrent and Delayed Nivolumab in Combination With nab-Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer. Front Oncol. 2019 Nov 26;9:1256. doi: 10.3389/fonc.2019.01256. eCollection 2019.
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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.
Chrystal Louis study director
Celgene Corporation
15 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 nab-Paclitaxel, Nivolumab and Gemcitabine in people with Breast Neoplasms and Pancreatic Neoplasms, run by Celgene at 15 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 34 inclusion and 22 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 31 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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?
Evaluate Dose Limiting Toxicity (DLT) of each combination regimen (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02309177, which also lists 1 linked publication.
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 31 May 2019.