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AzTrials

NeoplasmsPhase 1NCT00809133

Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours

A Phase 1 study testing Paclitaxel, Carboplatin and BIBW 2992 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in United Kingdom.

Completed

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

Official record
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Trial summary

The main purpose of this study is to assess the optimum dose of the following medications when they are given together: BIBW 2992 and paclitaxel (Taxol) BIBW 2992 and paclitaxel and bevacizumab (Avastin) BIBW 2992 and carboplatin BIBW 2992 and paclitaxel and carboplatin The effect of the different drug combinations… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
Paclitaxel, Carboplatin and BIBW 2992
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
2 sitesUnited Kingdom
Study dates
May 2007to Feb 2015
Phase
Phase 1
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

  • Male or female patients (patients) with a histologically confirmed diagnosis of malignancy that is now advanced, non-resectable and / or metastatic.
  • Age 18 years old or older.
  • Life expectancy of at least 3 months.
  • Written informed consent that is consistent with ICH-GCP guidelines.
  • Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  • Patients must have recovered from any previous surgery.
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  • Adequate organ function including the following:
  • Cardiac left ventricular function with resting ejection fraction greater than or equal to 50%
  • Absolute neutrophil count of greater than or equal to 1,500/microlitres; greater than 2000/microlitres for carboplatin
  • Platelets greater than or equal to 100,000/microlitres
  • Total bilirubin less than or equal to 1.5 mg/dl (<26 micromol /L, SI unit equivalent).
  • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal.
  • Creatinine less than or equal to 1.5 mg/dl (less than or equal to 132 micromol per liter, SI unit equivalent).
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment. Breast feeding mothers will be excluded since these agents may be toxic to infants.

Who cannot join

  • Active infectious disease
  • Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
  • GI tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
  • Significant cardiovascular disease (a history of congestive heart failure requiring therapy, a need for anti-arrhythmic therapy for a ventricular arrhythmia, unstable angina pectoris or myocardial infarction within 6 months prior to trial entry).
  • Patients who require full-dose anticoagulation.
  • Patients not completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC less than or equal to Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to 1st trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.
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  • Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least 8 weeks, no history of cerebral oedema or bleeding in the past 8 weeks and no requirement for steroids or anti-epileptic therapy
  • Persistent Grade 2 or greater neurotoxicity / neuropathy from any cause.
  • Patients on immunosuppressant therapy or with known HIV infection.
  • Treatment with any of the following within 4 weeks of starting trial medication, or during the trial, is not permitted: chemo-, immuno-, radio- (small field palliative radiotherapy is allowed provided this does not represent clear disease progression), biological therapies (including trastuzumab), hormone therapy (excluding LHRH agonists in prostate cancer, or bisphosphonates), or treatment with other investigational drugs.
  • Participation in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial.
  • Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past 4 weeks before start of therapy or concomitantly with this trial.
  • Patients with known or suspected hypersensitivity to any of the trial drugs, their excipients or similar compounds.
  • Patients unable to comply with the protocol.
  • Active alcohol or drug abuse.
  • Patients with known pre-existing interstitial lung disease
  • Additional exclusion criteria for patients recruited to cohorts B:
  • Patients with known or suspected hypersensitivity to bevacizumab, its excipients or Chinese hamster ovary cell products or other recombinant human or humanised antibodies.
  • Patients with brain metastases (a brain scan is not required unless the patient shows signs and symptoms of brain metastases and a brain scan is performed to rule out the presence of brain metastases).
  • Patients with intra-abdominal inflammation .
  • Major surgery within 4 weeks of starting treatment or any wound(s) deemed by the investigator to pose a significant risk to the patient in the event of delayed healing.
  • Prior treatment with anthracycline and/or prior radiation to the chest wall ( patients in these categories will only be entered into the study where the investigator deems the benefit to the patient to outweigh the risk).
  • Patients with any of the following conditions: significant hypertension, significant haemoptysis, known brian metastases, thrombotic or haemorrhagic disorders, INR greater than or equal to 1.5 abnormal PTT, therapeutic anti-coagulation, squamous non small cell lung cancer Additional exclusion criteria for patients recruited to cohorts C and D
  • Patients with severe myelosuppression; i.e. absolute neutrophil count less than 2000/microlitres
  • Patients with renal impairment (creatinine clearance less than 60ml per minute by Cockcroft-Gault equation)

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • 1200.12.4402 Boehringer Ingelheim Investigational Site

    London

  • 1200.12.4401 Boehringer Ingelheim Investigational Site

    Sutton

Other trials in United Kingdom

About this study

Official title: A Phase I Open Label Trial of Continuous Dosing With BIBW 2992 Combined With Paclitaxel and BIBW 2992 Combined With Paclitaxel and Bevacizumab, BIBW 2992 Combined With Carboplatin and BIBW 2992 Combined With Paclitaxel and Carboplatin in Patients With Advanced Solid Tumours

The main purpose of this study is to assess the optimum dose of the following medications when they are given together:

  • BIBW 2992 and paclitaxel (Taxol)
  • BIBW 2992 and paclitaxel and bevacizumab (Avastin)
  • BIBW 2992 and carboplatin
  • BIBW 2992 and paclitaxel and carboplatin The effect of the different drug combinations will also be assessed.
Conditions
Neoplasms
Being tested
Paclitaxel, Carboplatin, BIBW 2992, BIBW2992, Bevacizumab
Medical subject headings
Neoplasms

What participants receive

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

  • PaclitaxelDrug

    Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.

  • CarboplatinDrug

    AUC6 given on day 1 of 21 day cycle

  • BIBW 2992Drug

    Escalating dose cohorts

  • PaclitaxelDrug

    Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.

  • BIBW2992Drug

    MTD dose of part A

  • PaclitaxelDrug

    175mg/m2 given on Day 1 of 21 Day cycle

  • CarboplatinDrug

    AUC6 given on day 1 of 21 day cycle

  • BevacizumabDrug

    Escalating dose Cohorts - 5mg / kg, 7.5mg / kg and 10mg / kg given Day 1 and Day 15 of a 28 days cycle

  • BIBW 2992Drug

    Escalating dose cohorts

  • BIBW 2992Drug

    Escalating dose cohorts

Study groups in NCT00809133
Study groupRoleWhat they receive
Part AExperimentalBIBW2992 + Paclitaxel
Receives: Drug: BIBW 2992; Drug: Paclitaxel
Part BExperimentalBIBW2992 + Paclitaxel + Bevacizumab
Receives: Drug: Paclitaxel; Drug: BIBW2992; Drug: Bevacizumab
Part CExperimentalBIBW2992 + Carboplatin
Receives: Drug: Carboplatin; Drug: BIBW 2992
Part DExperimentalBIBW2992 +Paclitaxel + Carboplatin
Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: BIBW 2992

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

    Dose limiting toxicity (DLT) was defined as an Adverse Event (AE) or laboratory abnormality considered as related to study treatment.

    Measured: Cycle 1: 21 days (part C and D) or 28 days (part A and B)

  2. Maximum Tolerated Dose (MTD)

    The MTD of afatinib in selected combination treatments was defined as the highest dose at which no more than 1 out of 6 patients experienced DLTs during the first treatment cycle, i.e. the highest dose with a DLT incidence ≤17%. The MTD was determined separately for Afatinib in combination with Paclitaxel (part A), Afatinib in combination with Paclitaxel and Bevacizumab (part B), Afatinib and Carboplatin (part C), and Afatinib in combination with Paclitaxel and Carboplatin (part D).

    In part C, dose escalation was not continued beyond the dose level A40C6, due to safety and pharmacokinetic considerations and upon mutual agreement between the investigators and the sponsor. Formally, no MTD was determined, however a recommended phase II dose was determined and is presented here.

    0=not maximum tolerated dose, 1=is maximum tolerated dose

    Note, the depicted order of treatment groups is driven by dose level, not by the actual dosing steps.

    Measured: Cycle 1: 21 days (part C and D) or 28 days (part A and B)

Secondary outcomes (22)

  1. Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade

    Incidence and Intensity of AEs (Adverse Events) graded according to the maximum CTCAE (Common Toxicity Criteria for Adverse Events) grade based on the number of patients with AEs with CTCAE Grade 1-5.

    Measured: From first drug administration until the end of treatment cycle 1; 21 days (part C and D) or 28 days (part A and B)

  2. Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

    Area under the concentration-time curve of Afatinib in plasma at steady state.

    Measured: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

  3. Part A: Afatinib Cmax,ss on Day 15

    Maximum measured concentration of Afatinib in plasma at steady state.

    Measured: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

  4. Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15

    AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

    Measured: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  5. Part A: Paclitaxel Cmax on Day 1 and Day 15

    Maximum measured concentration of Paclitaxel in plasma.

    Measured: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  6. Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

    Area under the concentration-time curve of Afatinib in plasma at steady state.

    Measured: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. There were no analyzable patients for Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab.

  7. Part B: Afatinib Cmax,ss on Day 15

    Maximum measured concentration of Afatinib in plasma at steady state.

    Measured: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

  8. Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15

    AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

    Measured: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  9. Part B: Paclitaxel Cmax on Day 1 and Day 15

    Maximum measured concentration of Paclitaxel in plasma.

    Measured: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  10. Part B: Bevacizumab Plasma Concentration

    Bevacizumab plasma concentration after infusion of Bevacizumab 5mg/kg after end of 1st and 2nd infusion in Cycle 1.

    Measured: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  11. Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2

    AUCt,ss: Area under the concentration-time curve of Afatinib in plasma at steady state.

    Measured: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  12. Part C: Afatinib Cmax,ss in Cycle 2

    Maximum measured concentration of Afatinib in plasma at steady state.

    Measured: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  13. Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

    AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

    Measured: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00.

  14. Part C: Carboplatin Cmax in Cycle 1 and Cycle 2

    Maximum measured concentration of Carboplatin in plasma.

    Measured: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00

  15. Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.

    AUCt,ss: Area under the concentration-time curve of Afatinib at steady state.

    Measured: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  16. Part D: Afatinib Cmax,ss

    Maximum measured concentration of Afatinib in plasma at steady state.

    Measured: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  17. Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2

    AUC0-23: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 23 hours.

    Measured: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 23:00.

  18. Part D: Paclitaxel Cmax in Cycle 1 and 2

    Maximum measured concentration of Paclitaxel in plasma.

    Measured: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00

  19. Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

    AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

    Measured: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00

  20. Part D: Carboplatin Cmax in Cycle 1 and 2

    Maximum measured concentration of Carboplatin in plasma.

    Measured: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  21. Objective Tumour Response (Unconfirmed)

    Number of subjects with objective tumour response (unconfirmed).

    Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR).

    Measured: From first drug administration until the last trial drug administration, up to 1156 days.

  22. Objective Tumour Response (Confirmed)

    Number of subjects with confirmed objective tumour response.

    Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR). Objective response was to be confirmed by a second tumour assessment at least 4 weeks after the assessment of CR or PR.

    Measured: From first drug administration until the last trial drug administration, up to 1156 days.

Timeline

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

  1. First posted17 Dec 2008 (estimated)
  2. Study startMay 2007
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00809133
Sponsor's protocol ID
1200.12
Other IDs
2006-005005-55
Status last verified
Feb 2016
First submitted
16 Dec 2008
Last updated
14 Mar 2016

Publications

  • O'Brien MER, Sarker D, Bhosle J, Thillai K, Yap TA, Uttenreuther-Fischer M, Pemberton K, Jin X, Wiebe S, de Bono J, Spicer J. A phase I study to assess afatinib in combination with carboplatin or with carboplatin plus paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2018 Nov;82(5):757-766. doi: 10.1007/s00280-018-3661-1. Epub 2018 Aug 7.

    PubMed 30088048

  • Suder A, Ang JE, Kyle F, Harris D, Rudman S, Kristeleit R, Solca F, Uttenreuther-Fischer M, Pemberton K, Pelling K, Schnell D, de Bono J, Spicer J. A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours. Eur J Cancer. 2015 Nov;51(16):2275-84. doi: 10.1016/j.ejca.2015.07.041. Epub 2015 Aug 18.

    PubMed 26296295

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Paclitaxel, Carboplatin and BIBW 2992 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in United Kingdom.

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 25 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 14 Mar 2016. 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 Kingdom. 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?

Yes. Results are posted in the registry (first posted 14 Mar 2016). 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?

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) (time frame: Cycle 1: 21 days (part C and D) or 28 days (part A and B)). The study lists 2 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 NCT00809133, which also lists 2 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 14 Mar 2016.

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