Clinical Trials

MainTitle

Chemotherapy for Lung Cancer in HIV-positive Patients (CHIVA)

This study has been completed
Sponsor
Intergroupe Francophone de Cancerologie Thoracique


Information provided by (Responsible Party)
Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier
NCT01296113

First received: February 11, 2011
Last updated: September 19, 2017
Last Verified: September 2017
History of Changes
Purpose

Purpose

This is a phase II, multicenter, non-randomized, open-label study evaluating the combination of pemetrexed plus carboplatin in HIV-positive patients with lung cancer.

Condition Intervention Phase
Non-small Cell Lung Cancer
Hiv-positive

Drug : Chemotherapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial Evaluating the Efficacy and Safety of Carboplatin Plus Pemetrexed in Human Immunodeficiency Virus Positive (HIV+) Patients With Stage III (Not Amenable to Radiation or Inoperable) or Stage IV Nonsquamous Non Small Cell Lung Cancer

Further study details as provided by Intergroupe Francophone de Cancerologie Thoracique:

Primary Outcome Measures

  • Disease-Control rate after 4 cycles [ Time Frame: 3-weeks ]

Enrollment: 62
Study Start Date: May 2011
Study Completion Date: July 2017
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: A

Drug: Chemotherapy
  • Pemetrexed + Carboplatin
On D1 of a 21-day cycle:
    Pemetrexed 500 mg/m² IV in 10 minutes followed 30 minutes later by:
      Carboplatin AUC 5 in 30 minutes in 100 ml sterile water or 5% glucose or physiological serum. The carboplatin dose will be calculated by the Calvert formula with a target AUC of 5 mg/mL.min as follows:
      • Carboplatin dose in mg = 5 x (GFR + 25) GFR is estimated according to the MDRD equation for creatinine clearance
      • • 4 cycles total

      Detailed Description:

      The use of tritherapy in developed countries starting in 1996 led to a considerable reduction in AIDS mortality due to opportunistic infections and AIDS-defining cancers. However, increased life expectancies were accompanied by a diversification of the causes of death in HIV-infected individuals. In France between 2000 and 2005, non-AIDS-defining mortality rose from 53% to 64%: non-AIDS-defining cancers (apart from hepatocellular carcinoma) had the highest mortality rates, increasing from 11% to 17% in 2005, followed by liver disease (15% in 2005), cardiovascular disease (8% in 2005) and suicide (5%). Among all cancer-related deaths (AIDS- and non-AIDS-defining), the proportion due to non-AIDS-defining cancers (apart from hepatocellular carcinoma) increased from 38% to 50% and lung cancer (LC) accounted for 65% of deaths. Many epidemiological studies have demonstrated an elevated risk of LC in HIV-infected individuals HIV-positive subjects are younger at diagnosis of LC than the general population (45 versus 62 years). In the most recent studies, adenocarcinoma comprised 70% of cases. The prognosis of LC is worse in HIV-positive individuals. Some authors suggest that these poor outcomes may be related to interactions and additive toxicities of the cytotoxic and antiretroviral drugs. It is also likely that the disease is particularly aggressive. In the general population with a PS of 0 or 1 and under 70 years of age, bitherapy improves survival as compared to monotherapy. Survival is higher when the doublet comprises a platin. Since HIV-positive subjects with LC tend to be young, it is logical to offer them the best treatment which has demonstrated efficacy in the general population. In comparison to cisplatin, carboplatin causes less vomiting, nephrotoxicity and neurotoxicity. Survival is very slightly higher with cisplatin, but this comes at the cost of greater toxicity. Carboplatin is better tolerated in subjects with PS=2 or who are over 70 years of age
      The HIV-positive population is specific in that:

      • PS is more often altered but the subjects are young, which calls for a platin-based doublet.
      • HAART is essential and its absorption should not be compromised by repeated vomiting which is more severe with cisplatin.
      • Nephropathy occurs in 15-38% of cases; the causes are multifactorial and include the HIV virus itself and the antiretroviral drugs (Tenofovir®).
      • Peripheral neuropathy is frequently related to HIV or to the antiretroviral treatments (especially didanosine or stavudine (2010 YENI report)).
      • Premature ageing is seen in HIV-positive subjects; this exposes them to increased cardiovascular risk and a higher frequency of heart disease which can restrict the hyper-hydration required when using cisplatin.
      • In 2010, virtually all patients are treated on an ambulatory basis whereas in the past they would have been hospitalized. Carboplatin is administered in the day hospital of all the centers, but not cisplatin.
      • It is important to preserve an optimal quality of life during the first line of therapy
      in these patients whose life expectancy is such that very few will be eligible for a second round of therapy.
      Scagliotti published a phase III trial comparing cisplatin plus pemetrexed with cisplatin plus gemcitabine in subjects < 70 years old with advanced-stage NSCLC. Overall survival was identical in both arms but the toxicity profile was in favor of the pemetrexed arm. The combination of first-line carboplatin plus pemetrexed has been evaluated in several phase II trials, particularly in subjects with a poor PS. In contrast to the taxanes or vinorelbine, for example, pemetrexed is not metabolized by CYP450, which facilitates its use in combination with protease inhibitors and NNRTI, which respectively inhibit or induce the CYP450 system.
      Ancillary study BIO-IFCT-1001 will be made. Since the samples will be small, focus will be on the biomarkers associated with multiple or specific resistance to platinum salts or to pemetrexed, particularly those more specifically found in NSCLC of nonsquamous histology. Similarly, biomarkers for which IFCT pathologists have acquired an expertise will also be favored. This expertise mainly involves, on the one hand, detecting K-Ras mutations (15-25% of ADC) and RasSF1 methylation as well as TubIII expression by immunohistochemistry (IHC) and testing for mucosecretion by PAS diastase-resistant staining, and on the other hand, evaluating ERCC1 and/or MSH2 expression and thymidylate synthase (TS) expression by IHC.

      Eligibility

      Eligibility

      Ages Eligible for Study: 18 Years to 75 Years  
      Sexes Eligible for Study: All  
      Accepts Healthy Volunteers: No  

      Criteria

      Inclusion Criteria:

      • NSCLC histologically (highly recommended) and/or cytologically confirmed, stage III (non-irradiable or inoperable) or stage IV (according to 2009 TNM classification), with other than predominantly squamous histology
      • HIV seropositivity (previous or inaugural), irrespective of CD4 count or viral load
      • Presence of at least one measurable lesion (RECIST v1.1)
      • Subject having signed the informed consent form,
      • Subject who, in the investigator's opinion, will be able to comply with the requirements and constraints of the study
      • Age ≥ 18 years ≤ 75 years,
      • WHO performance status: 0, 1 or 2
      • Weight loss ≤ 10% of total body weight in the month before inclusion
      • Estimated life expectancy ≥ 1 month,
      • Covered by health insurance


      Exclusion Criteria:
      • Bronchial cancer already treated (other than endoscopic deobstruction)
      • Cancer which is amenable to surgery or radiation (curative),
      • Squamous cell lung cancer or mixed small cell and non-small cell cancer, small cell lung cancer
      • Creatinine clearance (MDRD) < 45 mL/min
      • Severe hypersensitivity to any of the study products or excipients
      • Severe disease or uncontrolled systemic disease (unstable or decompensated respiratory disease, cardiac, hepatic or renal disease, uncontrolled opportunistic infection)
      • Significant abnormality in CBC-platelets (Hb <9 g/dL, PNN <1500 / mm3, platelets < 100,000 / mm3)
      • Significant abnormality in liver tests (AST, ALT > 3x ULN, and <5 in case of liver metastases),
      • Women of childbearing age without effective contraception; pregnant or breastfeeding women
      • Subject who cannot take vitamin B12, folic acid or corticosteroids
      • Diffuse interstitial pneumonia
      • Any geographical situation or psychological condition that precludes full
      understanding and compliance with the protocol

      contacts and locations

      Contacts and Locations

      Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

      Please refer to this study by its ClinicalTrials.gov identifier: NCT01296113

      Locations

      France
      Centre Hospitalier du Pays d'Aix
      Aix-en-Provence, France
      Annemasse - CH
      Ambilly, France, 74100
      Annecy - CH
      Annecy, France, 74374
      Avignon - CH
      Avignon, France
      CH de la Côte Basque
      Bayonne, France
      CHU Besancon - Pneumologie
      Besancon, France, 25000
      Caen - CHU Côte de Nacre
      Caen, France, 14000
      CH Cahors
      Cahors, France
      CHU
      Clermont-Ferrand, France
      CH
      Colmar, France
      CH Compiègne - Pneumologie
      Compiègne, France
      Créteil - CHI
      Créteil, France, 94000
      CHU Grenoble - pneumologie
      Grenoble, France, 38000
      Le Mans - Centre Hospitalier
      Le Mans, France, 72000
      CH
      Longjumeau, France
      Hôpital de la Croix Rousse
      Lyon, France
      Hôpital Louis Pradel
      Lyon, France
      APHM - Hôpital Nord
      Marseille, France, 13000
      Montpellier - CHRU
      Montpellier, France, 34295
      Nevers - CH
      Nevers, France, 58033
      Centre Antoine Lacassagne
      Nice, France
      CHR d'Orléans La Source
      Orléans, France
      APHP - Hopital Tenon - Pneumologie
      Paris, France, 75020
      GH Paris Saint-Joseph
      Paris, France
      Hôpital Saint Antoine
      Paris, France
      Paris - Pitié-salpêtrière
      Paris, France
      Pau - CH
      Pau, France, 64046
      Centre François Magendie - hôpital du Haut-Lévèque
      Pessac, France
      HCL - Lyon Sud (Pneumologie)
      Pierre Bénite, France, 69495
      Reims - CHU
      Reims, France, 51092
      Rennes - CHU
      Rennes, France, 35033
      Saint Brieuc - CHG
      Saint Brieuc, France, 22000
      NHC - Pneumologie
      Strasbourg, France, 63000
      Suresnes - Hopital Foch
      Suresnes, France, 92151
      Thonon les bains - CH
      Thonon les bains, France, 74200
      Toulon - CHI
      Toulon, France, 83000
      CHU Toulouse - Pneumologie
      Toulouse, France
      Tourcoing - CH
      Tourcoing, France, 59208
      Tours - CHU
      Tours, France, 37000
      CH Valence
      Valence, France

      Sponsors and Collaborators

      Intergroupe Francophone de Cancerologie Thoracique

      Investigators

      Principal Investigator: Armelle LAVOLE, MD AP-HP, Hôpital Tenon
      More Information

      More Information

      Additional Information:

      IFCT official website

      Responsible Party: Intergroupe Francophone de Cancerologie Thoracique  
      ClinicalTrials.gov Identifier: NCT01296113   History of Changes  
      Other Study ID Numbers: IFCT-1001  
      Study First Received: February 11, 2011  
      Last Updated: September 19, 2017  

      Additional relevant MeSH terms:
      Lung Neoplasms
      Carcinoma, Non-Small-Cell Lung
      HIV Seropositivity
      Carboplatin
      Pemetrexed

      ClinicalTrials.gov processed this data on December 08, 2017
      This information is provided by ClinicalTrials.gov.