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Small Cell Lung CancerPhase 2NCT02963090

Pembrolizumab vs Topotecan in Patients With Small Cell Lung Cancer

A Phase 2 study testing Topotecan and Pembrolizumab in people with Small Cell Lung Cancer, run by Alliance Foundation Trials, LLC. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a multi-institutional, randomized, open-label phase II study of pembrolizumab compared to topotecan, administered to patients with SCLC who have progressed or relapsed after first-line treatment with etoposide and platinum. Patients will be randomized in a 2:1 fashion to receive pembrolizumab or topotecan. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Small Cell Lung Cancer
What is being tested?
Topotecan and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
20 May 2017to 20 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

  • In order to be eligible for participation in this trial, the patient must:
  • Have histologically or cytologically confirmed small cell lung cancer. Confirmation will be done at each participating site.
  • Have relapsed or progressed after only one prior chemotherapy regimen, which must have been an etoposide-platinum doublet. Eligible patients will be defined as follows:
  • "Sensitive" Disease: Patients who had one previous line of chemotherapy and relapsed after > 60 days of completion of treatment.
  • "Refractory" Disease: Patients with no response to first-line chemotherapy or progression >60 days after completing treatment.
  • Be ≥ 18 years of age on day of signing informed consent.
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  • Have a life expectancy of at least 3 months.
  • Have a performance status of ≤ 1 on the ECOG Performance Scale.
  • Have measurable disease based on RECIST 1.1.
  • Have a tumor tissue specimen available from either a core or excisional biopsy. The tumor specimen should be of adequate size and tumor cellularity to perform whole exome sequencing and immunohistochemistry. In subjects for whom newly obtained samples cannot be obtained (e.g. tumor inaccessible or safety concern), archived tissue may be submitted, if it otherwise satisfies all specimen criteria. Archival samples must have been obtained within 42 days prior to signing consent (please refer to section 12.1 of protocol).
  • Demonstrate adequate organ function as defined in Table 1.
  • Table 1. Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥8 g/dL (without transfusion) Renal Serum creatinine
  • OR
  • Glomerular Filtration Rate (GFR) ≤1.5 X upper limit of normal (ULN)
  • OR
  • GFR ≥60 mL/min for patient with creatinine levels > 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN
  • OR
  • Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
  • OR
  • ≤ 5 X ULN for patients with liver metastases Albumin ≥ 2.5 mg/dL
  • GFR should be calculated per institutional standards.
  • Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours of starting treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female patients of childbearing potential must be willing to an adequate method of contraception as outlined in Section 14.4.1 - Contraception for the course of the study through 120 days after the last dose of study medication (see Section 13.4.1). Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male patients must agree to use an adequate method of contraception as outlined in Section 14.4.1 - Contraception - starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Who cannot join

  • The patient must be excluded from participating in the trial if the patient:
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 14 days of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has had a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 14 days earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
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  • Has undergone major surgery, he/she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has known active central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
  • Has known carcinomatous meningitis.
  • Has an active autoimmune disease requiring systemic treatment in the past 2 years or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  • Has evidence of interstitial lung disease, or history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days prior to the planned first dose of study therapy.
  • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Hypersensitivity to pembrolizumab or any of its excipients.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Metro MN Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

Other trials in United States

About this study

Official title: A Randomized Phase II Study Evaluating Pembrolizumab vs Topotecan in the Second-Line Treatment of Patients With Small Cell Lung Cancer

This is a multi-institutional, randomized, open-label phase II study of pembrolizumab compared to topotecan, administered to patients with SCLC who have progressed or relapsed after first-line treatment with etoposide and platinum. Patients will be randomized in a 2:1 fashion to receive pembrolizumab or topotecan. Participants in the topotecan arm that progress will be allowed to cross-over to the pembrolizumab arm.

Read the detailed description

Patients who meet the eligibility criteria and are randomized to one of the treatment arms, will receive either topotecan alone intravenously at 1.25 mg/m2 on days 1 to 5 of a 21-day cycle or pembrolizumab alone administered intravenously at 200mg every 21 days.

During the study period, patients will be evaluated clinically by physical exam and with routine blood work every 21 days. Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4. Pre-specified adverse events of clinical interest include: 1) Grade ≥ 2 diarrhea, 2) Grade ≥ 2 colitis, 3) Grade ≥ 2 pneumonitis, 4) Grade ≥ 2 hepatitis 5) Grade ≥ 3 hypo- or hyperthyroidism.

Patients will be evaluated every 6 weeks (42 ± 7 days) with radiographic imaging to assess response to treatment. Investigators will make all treatment-based decisions using RECIST 1.1. Patients will continue to receive topotecan or pembrolizumab every three weeks until documented disease progression, unacceptable side effects, intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the patient, patient withdraws consent, pregnancy of the patient, non-compliance with trial treatment or procedure requirements or administrative reasons. Patients on the topotecan arm who progress on study will be allowed to cross-over to the pembrolizumab arm.

After the end of treatment, each patient will be followed for a minimum of 30 days for adverse event monitoring. Serious adverse events will be collected for up to 90 days after the end of treatment or 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier. Immune related serious adverse events will be followed for 90 days after end of treatment. Subjects who discontinue treatment for reasons other than disease progression will have posttreatment follow-up every 6 weeks for disease status until progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone contact every 3 months for overall survival until death or withdrawal of consent.

Although subjects will be enrolled regardless of PD-L1 status, subjects will be required to provide tissue of a tumor lesion (either archived tissue or a new biopsy before initiating therapy). Tumor samples will be required before initiating therapy (preferably a new specimen) and a repeat biopsy will be performed, if clinically feasible, on-treatment (during weeks 4 to 6) for those in the pembrolizumab arm and at the time of disease progression for those in the topotecan arm. PD-L1 expression status by immunohistochemistry will be determined on tumors at baseline, on treatment and at the time of topotecan progression. Numerous other correlative studies also will be performed, as outlined below. Peripheral blood mononuclear cell samples will be collected at screening, at day 1 of cycles 1, 2 and 3, and at the time of each imaging study (while on study), for characterization of T-cell phenotypes to understand how changes may correlate with clinical response.

Keywords
SCLC, small cell lung cancer, lung cancer, topotecan, pembrolizumab
Medical subject headings
Small Cell Lung Carcinoma, Lung Neoplasms

What participants receive

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

  • TopotecanDrug

    Also called hycamtin

    Topotecan at 1.25mg/m2 on days 1 to 5 every 21-days until progression of disease or unacceptable toxicities.

    Patients with progression of disease by RECIST 1.1 will be allowed cross over to receive pembrolizumab 200 mg IV every 21-days for up to 1 year until progression of disease or unacceptable toxicities.

  • PembrolizumabDrug

    Also called Keytruda, MK-3475

    200 mg IV every 21-days until progression of disease or unacceptable toxicities.

Study groups in NCT02963090
Study groupRoleWhat they receive
TopotecanActive comparatorTopotecan IV at 1265mg/m^2 Days 1-5 of every 21 day cycle
Receives: Drug: Topotecan; Drug: Pembrolizumab
PembrolizumabExperimentalPembrolizumab IV 200mg infusion Day 1 of every 21 day cycle
Receives: Drug: Pembrolizumab

What is being measured

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

  1. Progression Free Survival

    This phase II study will determine if there is a benefit in progression free survival (PFS) for SCLC patients receiving pembrolizumab (Experimental arm) as compared to topotecan (Control arm) in the second-line settingSCLC patients receiving pembrolizumab (Experimental arm) as compared to topotecan (Control arm) in the second-line setting. RECIST Version 1.1 was used in this study for assessment for tumor response. Progression (PD): At least one of the following must be true: a. At least one new malignant lesion, which also includes any lymph node that was normal at baseline (< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up. b. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD. In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.

    Measured: 4.2 months

Secondary outcomes (2)

  1. Overall Survival (OS)

    Overall survival will be calculated from the time a patient is registered until the time of death or discontinuation of followup

    Measured: 20 months

  2. Overall Response Percentage

    RECIST Version 1.1* will be used in this study for assessment for tumor response.

    Complete Response (CR): All of the following must be true:

    1. Disappearance of all target lesions.
    2. Each target lymph node must have reduction in short axis to < 1.0 cm. • Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD

    Measured: 4.2 months

Timeline

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

  1. First posted15 Nov 2016 (estimated)
  2. Study start20 May 2017
  3. Primary completion20 Jun 2019
  4. Study completion20 Aug 2019

Why it stopped: Lack of enrollment

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02963090
Sponsor's protocol ID
AFT-17
Status last verified
Feb 2023
First submitted
26 Oct 2016
Last updated
15 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Viale PH. The American Cancer Society's Facts & Figures: 2020 Edition. J Adv Pract Oncol. 2020 Mar;11(2):135-136. doi: 10.6004/jadpro.2020.11.2.1. Epub 2020 Mar 1. No abstract available.

    PubMed 33532112

  • Gaspar LE, McNamara EJ, Gay EG, Putnam JB, Crawford J, Herbst RS, Bonner JA. Small-cell lung cancer: prognostic factors and changing treatment over 15 years. Clin Lung Cancer. 2012 Mar;13(2):115-22. doi: 10.1016/j.cllc.2011.05.008. Epub 2011 Oct 14.

    PubMed 22000695

  • Varghese AM, Zakowski MF, Yu HA, Won HH, Riely GJ, Krug LM, Kris MG, Rekhtman N, Ladanyi M, Wang L, Berger MF, Pietanza MC. Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncol. 2014 Jun;9(6):892-6. doi: 10.1097/JTO.0000000000000142.

    PubMed 24828667

  • Ou SH, Ziogas A, Zell JA. Prognostic factors for survival in extensive stage small cell lung cancer (ED-SCLC): the importance of smoking history, socioeconomic and marital statuses, and ethnicity. J Thorac Oncol. 2009 Jan;4(1):37-43. doi: 10.1097/JTO.0b013e31819140fb.

    PubMed 19096304

  • Krug LM, Kris MG, Rosenzweig K, Travis W. Small cell and other neuroendocrine tumors of the lung. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncolology. 8th ed: Lippincott, Williams, and Wilkins; 2008.

  • von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. doi: 10.1200/JCO.1999.17.2.658.

    PubMed 10080612

  • Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P, Giaccone G, Schaefer B, Wanders J, Verweij J. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol. 1997 May;15(5):2090-6. doi: 10.1200/JCO.1997.15.5.2090.

    PubMed 9164222

  • Eckardt J, Gralla R, Palmer MC, et al. Topotecan as second-line therapy in patients with small cell lung cancer: a phase II study. Ann Oncol 1996;7:107 (abstr 513).

  • Depierre A, von Pawel J, Hans L, et al. Evaluation of Topotecan (Hycamtin) in relapsed small-cell lung cancer (SCLC): A multicenter phase II study. Lung Cancer 1997;18:35 (abstract 126).

  • Eckardt J, Depierre A, Ardizzoni A, von Pawel J, Fields SZ. Pooled analysis of topotecan in the second-line treatment of patients with sensitive small cell lung cancer. Proc Am Soc Clin Oncol 1997;16:452a (abstr 1624).

  • O'Brien M, Eckardt J, Ramlau R. Recent advances with topotecan in the treatment of lung cancer. Oncologist. 2007 Oct;12(10):1194-204. doi: 10.1634/theoncologist.12-10-1194.

    PubMed 17962613

  • Koschel R, Huber RM, Gatzemeier U, et al. Topotecan in Second-Line Treatment of Small Cell Lung Cancer Reduced Toxicity with Individualized Therapy. Lung Cancer 2000;29:42 (abstract 135).

  • Huber RM, Reck M, Gosse H, von Pawel J, Mezger J, Saal JG, Kleinschmidt R, Steppert C, Steppling H. Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer. Eur Respir J. 2006 Jun;27(6):1183-9. doi: 10.1183/09031936.06.00015605. Epub 2006 Feb 15.

    PubMed 16481389

  • Disis ML. Immune regulation of cancer. J Clin Oncol. 2010 Oct 10;28(29):4531-8. doi: 10.1200/JCO.2009.27.2146. Epub 2010 Jun 1.

    PubMed 20516428

  • Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002 Aug;8(8):793-800. doi: 10.1038/nm730. Epub 2002 Jun 24.

    PubMed 12091876

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Topotecan and Pembrolizumab in people with Small Cell Lung Cancer, run by Alliance Foundation Trials, LLC. at 2 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 25 inclusion and 23 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: stopped early, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 16 Sep 2022). 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?

Progression Free Survival (time frame: 4.2 months). 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 NCT02963090, which also lists 56 linked publications.

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 15 Feb 2023.

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