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

NCT00809133 | Completed Phase 1 Results

• 2 other identifiers: 1200.122006-005005-55
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 2

Brief 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 will also be assessed.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (22)

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

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

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

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

• Part A: Afatinib Cmax,ss on Day 15

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

• 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

  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.

• Part A: Paclitaxel Cmax on Day 1 and Day 15

  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.

Study Arms (4)

Part A

EXPERIMENTAL

BIBW2992 + Paclitaxel

Drug: BIBW 2992; Drug: Paclitaxel

Part B

EXPERIMENTAL

BIBW2992 + Paclitaxel + Bevacizumab

Drug: Paclitaxel; Drug: BIBW2992; Drug: Bevacizumab

Part C

EXPERIMENTAL

BIBW2992 + Carboplatin

Drug: Carboplatin; Drug: BIBW 2992

Part D

EXPERIMENTAL

BIBW2992 +Paclitaxel + Carboplatin

Drug: Carboplatin; Drug: Paclitaxel; Drug: BIBW 2992

Interventions

Paclitaxel DRUG

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

Part B

Carboplatin DRUG

AUC6 given on day 1 of 21 day cycle

Part D

BIBW 2992 DRUG

Escalating dose cohorts

Part A

BIBW2992 DRUG

MTD dose of part A

Part B

Bevacizumab DRUG

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

Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (2)

1200.12.4402 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1200.12.4401 Boehringer Ingelheim Investigational Site

Sutton, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 30088048 DERIVED

• 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.

  PMID: 26296295 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Paclitaxel; Carboplatin; Afatinib; Bevacizumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Amides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2008
• First Posted: December 17, 2008
• Study Start: May 1, 2007
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 14, 2016
• Results First Posted: March 14, 2016

Record last verified: 2016-02

Locations

GB (2)