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Lung CancerPhase 2NCT03256136

Nivolumab in Combination With Chemotherapy, or Nivolumab in Combination With Ipilimumab, in Advanced EGFR-Mutant or ALK-Rearranged NSCLC

A Phase 2 study testing Carboplatin, Nivolumab and pemetrexed in people with Lung Cancer, run by Massachusetts General Hospital at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This research study is studying a drug intervention as a possible treatment for lung cancer. The drugs involved in this study are: Nivolumab Carboplatin Pemetrexed Ipilimumab Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
Carboplatin, Nivolumab and pemetrexed
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
3 sitesUnited States
Study dates
22 Nov 2017to 19 Aug 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytologically confirmed advanced (stage IIIB or IV) non-small-cell lung cancer (NSCLC).
  • ALK-rearranged NSCLC: ALK rearrangement as assessed by ALK FISH, IHC, or next-generation sequencing (NGS). For ALK FISH, rearrangements must be detected in >15% of tumor cells.
  • EGFR-mutant NSCLC: EGFR activating gene mutation (e.g., L858R, exon 19 deletion) as well as a T790M mutation per local testing.
  • Presence of at least one measurable lesion as defined by RECIST v1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the completion of irradiation.
  • Prior treatment with appropriate tyrosine kinase inhibitors (TKIs) as follows:
  • ALK-positive NSCLC (cohorts B and D): Participants must have progressed on or after 1 or more next-generation ALK-TKI(s).
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  • EGFR-mutant NSCLC (cohorts A and C): Participants must have progressed on or after 1 or more third-generation, T790M mutant-selective EGFR-TKI(s).
  • Prior systemic chemotherapy requirements are as follows:
  • Nivolumab plus carboplatin and pemetrexed arms (cohorts A and B): NO prior systemic chemotherapy is allowed. NOTE: Prior adjuvant or neoadjuvant chemotherapy is allowed if received more than 12 months prior to the study.
  • Nivolumab plus ipilimumab arms (cohorts C and D): Participants must have received a platinum-based combination chemotherapy for their advanced lung cancer and either progressed on/after this chemotherapy or are intolerant. Only ONE line of chemotherapy is allowed. NOTE: Prior adjuvant or neoadjuvant chemotherapy does not count as an additional line of chemotherapy if received more than 12 months prior to the study.
  • Tumor tissue sample is required following the participant's last line of systemic therapy (TKI or chemotherapy). Tissue sample may be fresh (core needle, excisional, or incisional biopsy), or archival if obtained within 6 months prior to enrollment. There can have been no systemic therapy administered after the sample was obtained. If a tissue sample is available but it has been > 6 months and there has been no intervening therapy, the Principal Investigator may approve the sample after discussion. PD-L1 IHC testing will be performed on the tumor tissue, but positivity on the PD-L1 IHC testing is not required to enroll in the study.
  • Clinically asymptomatic and stable central nervous system (CNS) metastases are allowed (including untreated CNS metastases) if they have not required increasing doses of steroids or stable doses equivalent to prednisone > 10 mg daily within 2 weeks prior to study entry for CNS symptoms.
  • Prior palliative radiotherapy must have been completed at least 2 weeks prior to study entry.
  • Subjects must have been off any prior systemic anti-cancer treatment (including TKIs) for at least 5 half-lives of that drug.
  • Age ≥ 18 years old.
  • ECOG performance status of 0 or 1.
  • Life expectancy ≥ 12 weeks.
  • Screening laboratory values must meet the following criteria:
  • WBC ≥ 2.0 x 109/L
  • Neutrophils ≥ 1.5 x 109/L
  • Platelet ≥ 100 x 109/L
  • Hemoglobin ≥ 9/dL
  • Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance using Cockcroft-Gault formula ≥ 50 mL/min
  • Female CrCl = (140-age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
  • Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
  • Total bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's syndrome who may have total bilirubin < 3.0 mg/dL)
  • AST and ALT ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver metastases are present)
  • Females of child-bearing potential (defined as a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally post-menopausal for at least 24 consecutive months) must:
  • Have a negative serum or urine pregnancy test obtained within 24 hours prior to starting the investigational drug.
  • Not be breastfeeding.
  • Agree to use, and be able to comply with, highly effective contraception (failure rate less than 1% per year) without interruption while on study treatment plus 5 half-lives of nivolumab (half-life up to 25 days) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post treatment completion. Complete abstinence is acceptable if it is in line with the preferred and usual lifestyle of the patient. Period abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal implants, established and proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods from the options of diaphragm, cervical cap, vaginal sponge, and condom, or progesterone-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
  • Male subjects agree to remain abstinent or use a condom plus an additional contraceptive method that result in a failure rate of <1% per year during sexual contact with a female of childbearing potential while participating in the study, during dose interruptions, and for 31 weeks following the last dose of the study treatment, even if he has undergone a successful vasectomy. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable.
  • Subject has the ability to understand and provide signed informed consent.
  • Subject has the willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Who cannot join

  • Subjects previously treated with T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents.
  • Subjects with symptomatic brain metastases, carcinomatous meningitis, spinal cord compression, or intractable back pain due to compression of destructive mass.
  • Subjects with active, known, or suspected autoimmune disease. 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.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization (unless used to treat investigational drug-related adverse events). Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Subjects with interstitial lung disease or interstitial pneumonitis that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days prior to screening. No major surgery, other than diagnostic surgery, is allowed within 4 weeks prior to treatment in the study.
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  • Co-administration of anti-cancer therapies other than those administered in the study.
  • Subjects with other active malignancy requiring concurrent intervention.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). HIV-positive participants are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because there is the potential for pharmacokinetic interactions with combination antiretroviral therapy and study drugs.
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
  • Subjects with ≥ grade 2 peripheral neuropathy at enrollment per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
  • Pregnant or lactating women. Pregnant women are excluded from this study because the study drugs (i.e., nivolumab, ipilimumab, carboplatin, and pemetrexed) have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued.
  • Subjects currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug.
  • History of allergy or hypersensitivity to any study drugs or their excipients.
  • Any known clinically significant concomitant medical condition, laboratory abnormality, or psychiatric illness that, in the investigator's opinion, would prevent the subject from participating in the study, pose an unacceptable risk to the patient in this study, or interfere with the interpretation of safety results.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Massachusetts general Hospital

    Boston, Massachusetts, 02214

Other trials in United States

About this study

Official title: A Phase II Study of Nivolumab in Combination With Carboplatin and Pemetrexed, or Nivolumab in Combination With Ipilimumab, in Patients With Advanced, EGFR-mutant or ALK-rearranged, Non-Small Cell Lung Cancer

This research study is studying a drug intervention as a possible treatment for lung cancer.

The drugs involved in this study are:

  • Nivolumab
  • Carboplatin
  • Pemetrexed
  • Ipilimumab
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease.

The FDA (the U.S. Food and Drug Administration) has approved Nivolumab as a treatment for other types of cancers including lung cancer. However, the combination of Nivolumab with other drugs (such as those being tested in this study) has not been approved by the FDA as a treatment for this type of lung cancer.

The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of the drug Nivolumab in combination with standard of care chemotherapies, or in combination with Ipilimumab. Nivolumab and Ipilimumab are antibodies (a type of human protein) that are being tested to see if they will allow the body's immune system to work against tumor cells. This study is being done to see if Nivolumab and Ipilimumab, or Nivolumab and chemotherapy drugs (Carboplatin and Pemetrexed), are more effective against cancer when administered together.

These drugs are given as infusions. They are designed to "boost" the immune system's ability to suppress or kill cancer cells that are foreign to the human body.

Conditions
Lung Cancer
Keywords
Lung Cancer
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Paraplatin

    Chemotherapy

  • NivolumabDrug

    Also called Opdivo

    will allow the body's immune system to work against tumor cells

  • pemetrexedDrug

    Also called Alimta

    Chemo therapy

  • IpilimumabDrug

    Also called Yervoy

    will allow the body's immune system to work against tumor cells

Study groups in NCT03256136
Study groupRoleWhat they receive
Nivolumab Plus Ipilimumab EGFRExperimentalNivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks
Receives: Drug: Nivolumab; Drug: Ipilimumab
Nivolumab Plus Ipilimumab ALKExperimentalNivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks
Receives: Drug: Nivolumab; Drug: Ipilimumab
Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naiveExperimentalNivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Receives: Drug: Carboplatin; Drug: Nivolumab; Drug: pemetrexed
Nivolumab + Carboplatin + Pemetrexed ALK Chemo naiveExperimentalNivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Receives: Drug: Carboplatin; Drug: Nivolumab; Drug: pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR), Presented in Numbers of Participants

    Complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Up to approximately 2 years

Secondary outcomes (4)

  1. Disease Control Rate (DCR), Presented in Numbers of Participants

    The number of patients that achieved either complete response (CR), partial response (PR), or stable disease (SD) per RECIST version 1.1

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

    Measured: Up to approximately 2 years

  2. Progression Free Survival (PFS)

    Time from initiation of the study drugs to progression or death, whichever occurs first. Disease progression was assessed via RECIST 1.1

    Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study(this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progression).

    Confidence Intervals (CIs) were calculated using the Kaplan Meier (KM) method

    Measured: From the start of treatment until disease progression or death due to any cause, up to approximately 2 years

  3. Overall Survival (OS)

    Time from initiation of the study drugs to date of death due to any cause. CIs are the KM estimate CIs.

    Measured: From the start of treatment until death due to any cause, up to approximately 2 years

  4. Duration Of Response

    Time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    • Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study(this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progression).

    Measured: From the first documented response until disease progression or death, up to approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2017
  2. Study start22 Nov 2017
  3. Primary completion19 Aug 2019
  4. Study completion19 Aug 2019

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03256136
Sponsor's protocol ID
17-011
Status last verified
Oct 2020
First submitted
17 Aug 2017
Last updated
4 Nov 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Nivolumab and pemetrexed in people with Lung Cancer, run by Massachusetts General Hospital at 3 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 15 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 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR), Presented in Numbers of Participants (time frame: Up to approximately 2 years). 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 NCT03256136.

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 4 Nov 2020.

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