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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Intergroupe Francophone de Cancerologie Thoracique
Sponsor:
Information provided by (Responsible Party):
Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier:
NCT01296113
First received: February 11, 2011
Last updated: August 11, 2014
Last verified: August 2014
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-Control rate after 4 cycles [ Time Frame: 3-weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 62
Study Start Date: May 2011
Estimated Study Completion Date: January 2017
Estimated 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


  Hide Detailed Description

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
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

Contacts
Contact: Elodie AMOUR contact@ifct.fr
Contact: Franck MORIN contact@ifct.fr

Locations
France
Centre Hospitalier du Pays d'Aix Recruiting
Aix-en-Provence, France
Contact: Thierry ALLEGRE       contact@ifct.fr   
Annemasse - CH Recruiting
Ambilly, France, 74100
Contact: Dominique LEDUC, Dr       contact@ifct.fr   
Annecy - CH Recruiting
Annecy, France, 74374
Contact: stéphane HOMINAL, Dr       contact@ifct.fr   
CH de la Côte Basque Recruiting
Bayonne, France
Contact: Sophie SCHNEIDER       contact@ifct.fr   
CHU Besancon - Pneumologie Recruiting
Besancon, France, 25000
Contact: Virginie Westeel, Pr       contact@ifct.fr   
Caen - CHU Côte de Nacre Recruiting
Caen, France, 14000
Contact: Gerard ZALCMAN, Pr       contact@ifct.fr   
CH Cahors Recruiting
Cahors, France
Contact: Patricia BARRE       contact@ifct.fr   
CHU Recruiting
Clermont-Ferrand, France
Contact: Henri JANICOT       contact@ifct.fr   
CH Recruiting
Colmar, France
Contact: Lionel MOREAU       contact@ifct.fr   
CH Compiègne - Pneumologie Recruiting
Compiègne, France
Contact: Stéphanie DEHETTE       contact@ifct.fr   
Créteil - CHI Recruiting
Créteil, France, 94000
Contact: Isabelle Monnet, Dr       contact@ifct.fr   
CHU Grenoble - pneumologie Recruiting
Grenoble, France, 38000
Contact: Denis Moro-Sibilot, Pr       contact@ifct.fr   
Principal Investigator: Denis Moro-Sibilot, Pr         
Le Mans - Centre Hospitalier Recruiting
Le Mans, France, 72000
Contact: Olivier MOLINIER, Dr       contact@ifct.fr   
CH Recruiting
Longjumeau, France
Contact: Gérard OLIVIERO       contact@ifct.fr   
Hôpital de la Croix Rousse Recruiting
Lyon, France
Contact: Lize KIAKOUAMA-MALEKA, MD       contact@ifct.fr   
Hôpital Louis Pradel Recruiting
Lyon, France
Contact: Nicolas GIRARD, MD       contact@ifct.fr   
APHM - Hôpital Nord Recruiting
Marseille, France, 13000
Contact: Fabrice BARLESI, Dr       contact@ifct.fr   
Montpellier - CHRU Recruiting
Montpellier, France, 34295
Contact: Xavier Quantin, Dr       contact@ifct.fr   
Nevers - CH Recruiting
Nevers, France, 58033
Contact: Dominique Herman, Dr       contact@ifct.fr   
Centre Antoine Lacassagne Terminated
Nice, France
CHR d'Orléans La Source Recruiting
Orléans, France
Contact: Adrien DIXMIER       contact@ifct.fr   
APHP - Hopital Tenon - Pneumologie Recruiting
Paris, France, 75020
Contact: Armelle LAVOLE, MD       contact@ifct.fr   
GH Paris Saint-Joseph Recruiting
Paris, France
Contact: Jean-Pierre TREDANIEL       contact@ifct.fr   
Hôpital Saint Antoine Terminated
Paris, France
Paris - Pitié-salpêtrière Recruiting
Paris, France
Contact: Laurent TAILLADE, MD       contact@ifct.fr   
Pau - CH Recruiting
Pau, France, 64046
Contact: Aldo RENAULT, Dr       contact@ifct.fr   
Centre François Magendie - hôpital du Haut-Lévèque Recruiting
Pessac, France
Contact: Rémi VEILLON, Dr       contact@ifct.fr   
HCL - Lyon Sud (Pneumologie) Recruiting
Pierre Bénite, France, 69495
Contact: Pierre-Jean Souquet, Dr       contact@ifct.fr   
Reims - CHU Recruiting
Reims, France, 51092
Contact: Lidia PETIT, Dr       contact@ifct.fr   
Rennes - CHU Recruiting
Rennes, France, 35033
Contact: Hervé LENA, Dr       contact@ifct.fr   
Saint Brieuc - CHG Recruiting
Saint Brieuc, France, 22000
Contact: Daniel Coëtmeur, Dr       contact@ifct.fr   
NHC - Pneumologie Recruiting
Strasbourg, France, 63000
Contact: Philippe Fraisse, Dr       contact@ifct.fr   
Suresnes - Hopital Foch Recruiting
Suresnes, France, 92151
Contact: Hélène Doubre, Dr       contact@ifct.fr   
Thonon les bains - CH Recruiting
Thonon les bains, France, 74200
Contact: Philippe ROMAND, Dr       contact@ifct.fr   
Toulon - CHI Recruiting
Toulon, France, 83000
Contact: Clarisse Audigier-Valette, Dr       contact@ifct.fr   
CHU Toulouse - Pneumologie Recruiting
Toulouse, France
Contact: Christophe Herman, Dr       contact@ifct.fr   
Tourcoing - CH Recruiting
Tourcoing, France, 59208
Contact: Emilie PLUQUET, Dr       contact@ifct.fr   
Tours - CHU Recruiting
Tours, France, 37000
Contact: Eric Pichon, Dr       contact@ifct.fr   
CH Valence Recruiting
Valence, France
Contact: Robert RIOU       contact@ifct.fr   
Sponsors and Collaborators
Intergroupe Francophone de Cancerologie Thoracique
Investigators
Principal Investigator: Armelle LAVOLE, MD AP-HP, Hôpital Tenon
  More Information

Additional Information:
Publications:
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: August 11, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
HIV Seropositivity
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014